25th RCOphth Congress, President's Session paper:25 years of progress in medical retina

The quarter century since the foundation of the Royal College of Ophthalmologists has coincided with immense change in the subspecialty of medical retina, which has moved from being the province of a few dedicated enthusiasts to being an integral, core part of ophthalmology in every eye department. In age-related macular degeneration, there has been a move away from targeted, destructive laser therapy, dependent on fluorescein angiography to intravitreal injection therapy of anti-growth factor agents, largely guided by optical coherence tomography. As a result of these changes, ophthalmologists have witnessed a marked improvement in visual outcomes for their patients with wet age-related macular degeneration (AMD), while at the same time developing and enacting entirely novel ways of delivering care. In the field of diabetic retinopathy, this period also saw advances in laser technology and a move away from highly destructive laser photocoagulation treatment to gentler retinal laser treatments. The introduction of intravitreal therapies, both steroids and anti-growth factor agents, has further advanced the treatment of diabetic macular oedema. This era has also seen in the United Kingdom the introduction of a coordinated national diabetic retinopathy screening programme, which offers an increasing hope that the burden of blindness from diabetic eye disease can be lessened. Exciting future advances in retinal imaging, genetics, and pharmacology will allow us to further improve outcomes for our patients and for ophthalmologists specialising in medical retina, the future looks very exciting but increasingly busy.

Simultaneous en-face imaging of two layers in human retina by low-coherence reflectometry

We show that with a fiberized multiple Michelson-interferometer-type configuration, transverse images from several layers in the human eye can be simultaneously obtained. We demonstrate the principle by producing simultaneous 100×100 pixel en-face images of a 4 mm×4 mm region on a postmortem retina for two depth positions 250 µm apart.

Transversal and longitudinal images from the retina of the living eye using low coherence interferometry

An optical coherence tomography (OCT) system to produce both longitudinal and transversal images of the in vivo human eye is presented. For the first time, OCT transversal images collected from the living eye at 50-µm depth steps show details unobtainable with the state-of-the-art scanning laser ophthalmoscope. Images of up to 3×3?mm are produced from the retina in less than a second. For images larger than 1.6×1.6?mm, a path modulation is introduced by the galvanometric scanning mirror and is used as an effective phase modulation method.

Distribution of light in the human retina under natural viewing conditions

Age-related macular degeneration (AMD) is the leading cause of blindness inAmerica. The fact that AMD wreaks most of the damage in the center of the retina raises the question of whether light, integrated over long periods, is more concentrated in the macula. A method, based on eye-tracking, was developed to measure the distribution of light in the retina under natural viewing conditions. The hypothesis was that integrated over time, retinal illumination peaked in the macula. Additionally a possible relationship between age and retinal illumination was investigated. The eye tracker superimposed the subject's gaze position on a video recorded by a scene camera. Five informed subjects were employed in feasibility tests, and 58 naïve subjects participated in 5 phases. In phase 1 the subjects viewed a gray-scale image. In phase 2, they observed a sequence of photographic images. In phase 3 they viewed a video. In phase 4, they worked on a computer; in phase 5, the subjects walked around freely. The informed subjects were instructed to gaze at bright objects in the field of view and then at dark objects. Naïve subjects were allowed to gaze freely for all phases. Using the subject's gaze coordinates, and the video provided by the scene camera, the cumulative light distribution on the retina was calculated for ∼15° around the fovea. As expected for control subjects, cumulative retinal light distributions peaked and dipped in the fovea when they gazed at bright or dark objects respectively. The light distribution maps obtained from the naïve subjects presented a tendency to peak in the macula for phases 1, 2, and 3, a consistent tendency in phase 4 and a variable tendency in phase 5. The feasibility of using an eye-tracker system to measure the distribution of light in the retina was demonstrated, thus helping to understand the role played by light exposure in the etiology of AMD. Results showed that a tendency for light to peak in the macula is a characteristic of some individuals and of certain tasks. In these situations, risk of AMD could be increased. No significant difference was observed based on age.

Selenium Distribution in the Human Retina

Selenium is known to occur in the enzyme, glutathione peroxidase, and plays an important role as an antioxidant. The objective of this investigation was to determine if amounts of selenium are selectively accumulated in different regions of the retina or uniformly distributed with eccentricity. 20 human retinas were analyzed for selenium. 18 of these were sectioned into a disc and two concentric annuli centered on the fovea using trephines having diameters of 3, 11, and 21 mm. The sections had areas of7.1, 93, and 343 mm2, respectively. Corresponding sections of these retinas were combined and analyzed together in sets of n = 5 and n = 11. For two donors, the whole retina of one eye was analyzed for selenium and the other retina was sectioned for analysis as described above. Selenium was determined using atomic fluorescence spectroscopy after digestion of the retinal tissues in nitric acid. The two whole retinas were found to have an average of 0.89 ± 0.49 pmoles/mm2 of selenium as compared to the companion which had 0.84 ± 0.28 pmoles/mm2 as determined from the sum of the selenium amounts measured in the individual sections. The inner, medial, and outer portions of these two sectioned retinas were found to contain an average of5.28 ± 1.1, 1.28 ± 0.44, 0.63 ± 0.22 pmoles/mm2, respectively. The five retinas that were sectioned and pooled for analysis were found to have average amounts of3.64, 1.26, and 0.56 pmoles/mm2 • The 11-sectioned retinas were found to have 1.16, 0.61, and 0.38 pmoles/mm2 respectively in the same three sections. This limited data set indicates that selenium is not uniformly distributed within the human retina but rather concentrated to a greater extent within the macula. If confirmed, these data would support the hypothesis that selenium may be an important antioxidant involved in protection of the macula from radical oxidants.

Determinantes genéticos e ambientais das doenças hipertensivas da gravidez

The development of complex diseases such as preeclampsia are determined by both environmental and genetic factors, but there is also interaction among these factors. Preeclampsia is a pregnancy-specific disorder characterized by de-novo hypertension and proteinuria after 20th week of gestation. There is a broad spectrum of clinical presentations related to hypertensive disorders of pregnancy (HDP) that can range from mild preeclampsia to eclampsia (seizures) or HELLP syndrome (Hemolysis, Elevation of Liver enzymes, Low Platelets). Those clinical outcomes might be linked to different pathological mechanisms. Our work aims to identify factors (i.e. genes and environmental) associated with the HDP’s clinical spectrum. Using a case-control approach, we selected a total of 1498 pregnant women for epidemiological and genetic studies, encompassing 755 normotensive (control); 518 preeclampsia; 84 eclampsia; and 141 HELLP. Women were genotyped for 18 SNPs across 5 candidate genes (FLT1, ACVR2A, ERAP1, ERAP2 and LNPEP). For the environmental factors, we found maternal age, parity status and pre-gestational body mass index as important risk factors associated with disease. Genes were associated in a phenotype-specific manner: ACVR2A with early preeclampsia (rs1424954, p=0.002); FLT1 with HELLP syndrome (rs9513095, p=0.003); and ERAP1 with eclampsia (rs30187, p=0.03). Our results suggest that different genetic mechanisms along with specific environmental factors might determine the clinical spectrum of HDP. In addition, phenotype refinement seems to be an essential step in the search for complex disease genes

Características bioativas, funcionais e efeito protetor do resíduo desidratado de camu-camu (Myrciaria dubia H.B.K. (McVaugh)) sobre doenças degenerativas utilizando modelos in vivo C. elegans

Camu-camu (Myrciaria dubia H.B.K. (McVaugh)) is a native Amazon fruit, recognized worldwide as one of the main natural sources of ascorbic acid. Due to its great acidity, this fruit is generally consumed after processing into juice or as ingredient in food preparations. As a co-product of the camu-camu processing, a significant amount of agroindustrial residue is generated. Despite the studies showing the bioactive value and biological potential of the fruit, few studies have approached the possible processing techniques, transformation and preservation of camu-camu fruits and its agroindustrial pomace. Therefore, the present work has the objective of evaluating two different drying processes applied to camu-camu pomace (peel and seeds with residual pulp), freeze drying and hot air drying, in order to obtain a functional fruit product. This thesis was divided into three stages: the first one shows the studies related to the freeze drying and hot air drying, where we demonstrated the impact of the selected drying techniques on the bioactive components of camu-camu, taking the fresh pomace as the control group. Among the investigated conditions, the groups obtained at 50ºC and 4 m/s (SC50) and 80ºC and 6 m/s (SC80) were selected as for further studies, based on their ascorbic acid final content and Folin-Ciocalteau reducing capacity. In addition to SC50 and SC80, the fresh pomace (RF) and freeze dried (RL) samples were also evaluated in these further stages of the research. Overall, the results show higher bioactive concentration in the RF samples, followed by RL, SC50 and SC80. On the second step of the research, the antioxidant, antimicrobial and antienzymatic activities were evaluated and the same tendency was observed. It was also reported, for the first time in the literature, the presence of syringic acid in dried camu-camu pomace. In the third and final stage of the research, it was investigated the effect of dried camu-camu on aging and neuroprotective disorders, using the in vivo model C.elegans. It was observed that camu-camu extracts were able to modulate important signaling genes relevant to thermal and oxidative stresses (p < 0.05). The polar acid, polar basic and polar neutral fractions obtained from the low molecular extracts of SC50 were able to extend the lifespan of wild type N2 C. elegans in 20% and 13% (p < 0.001). Results also showed that the paralysis induced by the β1-42 amyloid was significantly (p < 0.0001) retarded in CL4176 worms. Similarly, the camu-camu extracts attenuated the dopaminergic induction associated to Parkinson’s disease. Finally, a global analysis of the data presented here reveal that the camu-camu pomace, a co-product obtained from the industrial processing of a native Brazilian fruit, is a relevant natural source of health relevant compounds. This thesis, shows for the first time, the multifunctionality of camu-camu pomace, a natural resource still underexploited for scientific, commercial and technological purposes.

Três alternativas estocásticas para modelar morbimortalidade por doenças respiratórias e cardiovasculares via variáveis atmosféricas

Climate and air pollution, among others, are responsible factors for increase of health vulnerability of the populations that live in urban centers. Climate changes combined with high concentrations of atmospheric pollutants are usually associated with respiratory and cardiovascular diseases. In this sense, the main objective of this research is to model in different ways the climate and health relation, specifically for the children and elderly population which live in São Paulo. Therefore, data of meteorological variables, air pollutants, hospitalizations and deaths from respiratory and cardiovascular diseases a in 11-year period (2000-2010) were used. By using modeling via generalized estimating equations, the relative risk was obtained. By dynamic regression, it was possible to predict the number of deaths through the atmospheric variables and the betabinomial-poisson model was able to estimate the number of deaths and simulate scenarios. The results showed that the risk of hospitalizations due to asthma increases approximately twice for children exposed to high concentrations of particulate matter than children who are not exposed. The risk of death by acute myocardial infarction in elderly increase in 3%, 6%, 4% and 9% due to high concentrations CO, SO2, O3 and PM10, respectively. Regarding the dynamic regression modeling, the results showed that deaths by respiratory diseases can be predicted consistently. The beta-binomial-poisson model was able to reproduce an average number of deaths by heart insufficiency. In the region of Santo Amaro the observed number was 2.462 and the simulated was 2.508, in the Sé region 4.308 were observed and 4.426 simulated, which allowed for the generation of scenarios that may be used as a parameter for decision. Making with these results, it is possible to contribute for methodologies that can improve the understanding of the relation between climate and health and proved support to managers in environmental planning and public health policies.

Perfil sociodemográfico dos idosos nas capitais do Nordeste e a mortalidade por doenças crônico-degenerativas desse segmento populacional em Natal (RN)

Population aging is a global demographic trend. This process is a reality that merits attention and importance in recent years, and cause considerable impact in terms of greater demands on the health sector, social security and special care and attention from families and society as a whole. Thus, in the context of addressing the consequences of demographic transition, population aging is characterized as a major challenge for Brazilian society. Therefore, this study was conducted in two main objectives. In the first article, variables of socioeconomic and demographic contexts were employed to identify multidimensional profiles of elderly residents in the Northeast capitals, from specific indicators from the 2010 Census information Therefore, we used the Grade of Membership Method (GoM), whose design profiles admits that an individual belongs to different degrees of relevance to multiple profiles in order to identify socioeconomic and demographic factors associated with living conditions of the elderly in the Northeastern capitals. The second article examined the possible relationship between mortality from chronic diseases and socio-economic indicators in the elderly population, of the 137 districts in Natal, broken down by ten-year age groups (60 to 69 years, 70-79 years and 80 and over. The microdata from the Mortality Information System (SIM), was used, provided by the Health Secretariat of Christmas, and population information came from the Population Census 2010. The method refers to the Global and Local Index neighborhood logic (LISA) Moran, whose spatial distribution from the choropleth maps allowed us to analyze the mortality of the elderly by neighborhoods, according to socioeconomic and demographic indicators, according to the presence of special significance. In the first article, the results show the identification of three extreme profiles. The Profile 1 which is characterized by median socioeconomic status and contributes 35.5% of elderly residents in the area considered. The profile 2 which brings together seniors with low socioeconomic status characteristics, with a percentage of 24.8% of cases. And the Profile 3 composing elderly with features that reveal better socioeconomic conditions, about 29.7% of the elderly. Overall, the results point to poor living conditions represented by the definition of these profiles, mainly expressed by the results observed in more than half of the northeastern elderly experience a situation of social vulnerability given the large percentage that makes up the Profile 1 and Profile 2, adding 60% of the elderly. In the second article, the results show a higher proportion of elderly concentrated in the neighborhoods of higher socioeconomic status, such as Petrópolis and LagoaSeca. Mortality rates, according to the causes of death and standardized by the empirical Bayesian method were distributed locally as follows: Neoplasms (Reis Santos, New Discovery, New Town, Grass Soft and Ponta Negra); Hypertensive diseases (Blue Lagoon, Potengi, Redinha, Reis Santos, Riverside, Lagoa Nova, Grass Soft, Neópolis and Ponta Negra); Acute Myocardial Infarction (Northeast, Guarapes and grass Soft); Cerebrovascular diseases (Petrópolis and Mother Luiza); Pneumonia (Ribeira, Praia do Meio, New Discovery, Grass Soft and Ponta Negra); Chronic Diseases of the Lower Way Airlines (Igapó, Northeast and Thursdays). The present findings at work may contribute to other studies on the subject and development of specific policies for the elderly.

Perfil sociodemográfico dos idosos nas capitais do Nordeste e a mortalidade por doenças crônico-degenerativas desse segmento populacional em Natal (RN)

Population aging is a global demographic trend. This process is a reality that merits attention and importance in recent years, and cause considerable impact in terms of greater demands on the health sector, social security and special care and attention from families and society as a whole. Thus, in the context of addressing the consequences of demographic transition, population aging is characterized as a major challenge for Brazilian society. Therefore, this study was conducted in two main objectives. In the first article, variables of socioeconomic and demographic contexts were employed to identify multidimensional profiles of elderly residents in the Northeast capitals, from specific indicators from the 2010 Census information Therefore, we used the Grade of Membership Method (GoM), whose design profiles admits that an individual belongs to different degrees of relevance to multiple profiles in order to identify socioeconomic and demographic factors associated with living conditions of the elderly in the Northeastern capitals. The second article examined the possible relationship between mortality from chronic diseases and socio-economic indicators in the elderly population, of the 137 districts in Natal, broken down by ten-year age groups (60 to 69 years, 70-79 years and 80 and over. The microdata from the Mortality Information System (SIM), was used, provided by the Health Secretariat of Christmas, and population information came from the Population Census 2010. The method refers to the Global and Local Index neighborhood logic (LISA) Moran, whose spatial distribution from the choropleth maps allowed us to analyze the mortality of the elderly by neighborhoods, according to socioeconomic and demographic indicators, according to the presence of special significance. In the first article, the results show the identification of three extreme profiles. The Profile 1 which is characterized by median socioeconomic status and contributes 35.5% of elderly residents in the area considered. The profile 2 which brings together seniors with low socioeconomic status characteristics, with a percentage of 24.8% of cases. And the Profile 3 composing elderly with features that reveal better socioeconomic conditions, about 29.7% of the elderly. Overall, the results point to poor living conditions represented by the definition of these profiles, mainly expressed by the results observed in more than half of the northeastern elderly experience a situation of social vulnerability given the large percentage that makes up the Profile 1 and Profile 2, adding 60% of the elderly. In the second article, the results show a higher proportion of elderly concentrated in the neighborhoods of higher socioeconomic status, such as Petrópolis and LagoaSeca. Mortality rates, according to the causes of death and standardized by the empirical Bayesian method were distributed locally as follows: Neoplasms (Reis Santos, New Discovery, New Town, Grass Soft and Ponta Negra); Hypertensive diseases (Blue Lagoon, Potengi, Redinha, Reis Santos, Riverside, Lagoa Nova, Grass Soft, Neópolis and Ponta Negra); Acute Myocardial Infarction (Northeast, Guarapes and grass Soft); Cerebrovascular diseases (Petrópolis and Mother Luiza); Pneumonia (Ribeira, Praia do Meio, New Discovery, Grass Soft and Ponta Negra); Chronic Diseases of the Lower Way Airlines (Igapó, Northeast and Thursdays). The present findings at work may contribute to other studies on the subject and development of specific policies for the elderly.

A crença sobre a morte e o coping religioso-espiritual em pacientes internados com doenças crônicas

The human being is understood as an integral being, complex, which has multiple dimensions: social, biological, psychological, anthropological, spiritual and others. As its biological dimension, the man presents the possibility of physical illness, which means that the body requires care. The sick away from humans in health and safety conditions, approaching them directly from the finitude and vulnerability condition, leading us to contact the major uncertainties of life: suffering of disease and death. Religiosity and spirituality are important coping strategy for human when faced with borderline situations. When people turn to religion to cope with stress is the religious and spiritual coping. The objective of this research was to evaluate the relationship between the views on death and the religious-spiritual coping in patients with chronic diseases hospitalized. The study included ten patients hospitalized for chronic disease complications Medical Clinic Unit of a public hospital in the city of Uberlândia/MG. two psychological scales were used: Scale Religious-Spiritual Coping Brief (CRE-Brief Scale) and Scale Brief Diverse Perspectives of Death and a structured interview (audiogravada) on the subject of death and religious and spiritual coping. The results indicated that 80% of the sample (N = 8) consisted of patients hospitalized due to chronic diseases, while 20% accounted for patients with AIDS complications. Analyzing the results of scale CRE-Brief, it emphasizes the use of strategies of religious and spiritual coping by participants as compared to CRE Total, all study participants had average or high scores for this index, with a low utilization CRE negative and average utilization CRE Positive. Regarding views on death, the results obtained by the Different Perspectives Quick Scale on Death suggest that this sample agrees with the view death as something that is part of the natural cycle of life (M8 - Death as a natural end) and features the prospect of death as uncertainty, mystery and ignorance (M4 - death as Unknown). The correlations between the measures the factors and items of CRE-Bref and dimensions of Short scales on different perspectives of Death notes the prevalence of correlations of M4 dimensions - Death as unknown and M8 - Death as a natural order to the creditor scale soon. In the interview analysis revealed a positive influence of religion/ spirituality on health, from the perspective of the respondent, highlighting the protection promoted by religion. It also noticed the use of prayer as a coping strategy of hospitalization and illness. Regarding the interview about the topic of death, there was a predominance of issues related to "afterlife", "unknown" and "abandonment", which are associated with the visions of death and mystery and death as a natural end. In the interviews there belief clues about death as a terrifying mystery connected, so the unknown and the feeling of fear on the same. The experience of illness can therefore be considered as a source of vulnerability, since it is present personal perception of danger (external) - own illness and possible death, especially in those patients undergoing ICU - and where control is insufficient for the sense of security, since the hospital providing care to the patient are delegated to third parties and patients assume a passive role. This fact is important and relevant to health professionals who deal daily with patients hospitalized for chronic diseases, since the recourse to religion and spirituality as a coping strategy that psychic movement was not constituted in a form of negative distance or even denial of health condition. On the contrary, it refers to a movement in search of comfort and security provided by the religion and spirituality.

Caracterización de un modelo murino de glaucoma: implicación funcional de la señalización del receptor P2X7 en procesos neurodegenerativos de la retina

El glaucoma es una de las causas más comunes de discapacidad visual y una de las enfermedades neurodegenerativas oculares más frecuentes de pérdida irreversible de visión. La afectación originada en la retina se caracteriza por la degeneración de las células ganglionares y la pérdida de axones. La presión intraocular es un factor de riesgo importante en el glaucoma, entre otros factores, implicando mecanismos bioquímicos que desencadenan la muerte de las células ganglionares. El ratón DBA/2J es un modelo de hipertensión ocular y de degeneración de las células ganglionares de la retina (CGR). Las características principales de éste son la dispersión del pigmento del iris (IPD) y la atrofia del estroma del iris (ISA) que conducen a la patogénesis del glaucoma. Los mecanismos bioquímicos que comprometen al sistema purinérgico en procesos patológicos como la degeneración glaucomatosa han sido estudiados en los últimos años, siendo de gran relevancia como posibles dianas farmacológicas para el tratamiento de diferentes neuropatías. Los receptores P2X comprenden una familia de siete canales iónicos de membrana activados por ligando (P2X1-7) que se activan por el ATP extracelular (ATPe). En particular, los receptores P2X7 podrían estar involucrados en la regulación de la transmisión sináptica y la muerte neuronal en la retina. Además, la excitotoxicidad mediada por ATP a través de la activación del receptor P2X7 sugiere su posible implicación en la degeneración neuronal y la pérdida de la función visual en las retinas glaucomatosas. Tan importante como la presencia de este receptor purinérgico es estudiar los niveles de ATP extracelular de la retina, así como evaluar los cambios en la expresión del transportador de nucleótidos vesicular (VNUT) y los niveles de ecto-nucleotidasa (E-NPP1) en este modelo murino de glaucoma durante el desarrollo de la enfermedad...

Enhancing the Visualization of the Peripheral Retina with Wide Field-of-View Optical Coherence Tomography

The goal of my Ph.D. thesis is to enhance the visualization of the peripheral retina using wide-field optical coherence tomography (OCT) in a clinical setting.

OCT has gain widespread adoption in clinical ophthalmology due to its ability to visualize the diseases of the macula and central retina in three-dimensions, however, clinical OCT has a limited field-of-view of 300. There has been increasing interest to obtain high-resolution images outside of this narrow field-of-view, because three-dimensional imaging of the peripheral retina may prove to be important in the early detection of neurodegenerative diseases, such as Alzheimer's and dementia, and the monitoring of known ocular diseases, such as diabetic retinopathy, retinal vein occlusions, and choroid masses.

Before attempting to build a wide-field OCT system, we need to better understand the peripheral optics of the human eye. Shack-Hartmann wavefront sensors are commonly used tools for measuring the optical imperfections of the eye, but their acquisition speed is limited by their underlying camera hardware. The first aim of my thesis research is to create a fast method of ocular wavefront sensing such that we can measure the wavefront aberrations at numerous points across a wide visual field. In order to address aim one, we will develop a sparse Zernike reconstruction technique (SPARZER) that will enable Shack-Hartmann wavefront sensors to use as little as 1/10th of the data that would normally be required for an accurate wavefront reading. If less data needs to be acquired, then we can increase the speed at which wavefronts can be recorded.

For my second aim, we will create a sophisticated optical model that reproduces the measured aberrations of the human eye. If we know how the average eye's optics distort light, then we can engineer ophthalmic imaging systems that preemptively cancel inherent ocular aberrations. This invention will help the retinal imaging community to design systems that are capable of acquiring high resolution images across a wide visual field. The proposed model eye is also of interest to the field of vision science as it aids in the study of how anatomy affects visual performance in the peripheral retina.

Using the optical model from aim two, we will design and reduce to practice a clinical OCT system that is capable of imaging a large (800) field-of-view with enhanced visualization of the peripheral retina. A key aspect of this third and final aim is to make the imaging system compatible with standard clinical practices. To this end, we will incorporate sensorless adaptive optics in order to correct the inter- and intra- patient variability in ophthalmic aberrations. Sensorless adaptive optics will improve both the brightness (signal) and clarity (resolution) of features in the peripheral retina without affecting the size of the imaging system.

The proposed work should not only be a noteworthy contribution to the ophthalmic and engineering communities, but it should strengthen our existing collaborations with the Duke Eye Center by advancing their capability to diagnose pathologies of the peripheral retinal.

Diabetes Impairs the Aldehyde Detoxifying Capacity of the Retina

Purpose: We studied whether the accumulation of advanced lipoxidation end-products (ALEs) in the diabetic retina is linked to the impairment of lipid aldehyde detoxification mechanisms.

Methods: Retinas were collected from nondiabetic and diabetic rats and processed for conventional and quantitative RT-PCR (qRT-PCR), Western blotting, immunohistochemistry, and aldehyde dehydrogenase (ALDH) activity assays. The effect of the ALDH1a1 inhibitor, NCT-501, on ALE accumulation and cell viability in cultured Müller glia also was investigated.

Results: The rat retina expressed a range of lipid aldehyde detoxifying ALDH and aldo-keto reductase (AKR) genes. In diabetes, mRNA levels were reduced for 5 of 9 transcripts tested. These findings contrasted with those in the lens and cornea where many of these enzymes were upregulated. We have reported previously accumulation of the acrolein (ACR)-derived ALE, FDP-lysine, in retinal Müller glia during diabetes. In the present study, we show that the main ACR-detoxifying ALDH and AKR genes expressed in the retina, namely, ALDH1a1, ALDH2, and AKR1b1, are principally localized to Müller glia. Diabetes-induced FDP-lysine accumulation in Müller glia was associated with a reduction in ALDH1a1 mRNA and protein expression in whole retina and a decrease in ALDH1a1-immunoreactivity specifically within these cells. No such changes were detected for ALDH2 or AKR1b1. Activity of ALDH was suppressed in the diabetic retina and blockade of ALDH1a1 in cultured Müller glia triggered FDP-lysine accumulation and reduced cell viability.

Conclusions: These findings suggest that downregulation of ALDH and AKR enzymes, particularly ALDH1a1, may contribute ALE accumulation in the diabetic retina.