[Recueil].

Capitulare ecclesiasticum (1-7v). - Capitula legibus addenda (7v-14v). - Capitula per se scibenda (14v-16v). - Capitulare missorum (16v-20). "Domine Deus omnipotens propitius est omni peccatori..." [Ajout du Xe s.] (20v). - Collectio capitularium Ansegisi (21-40v). - Lex salica (41-83v). Les cahiers des ff. 1-20 et 41-83 faisaient partie du même ms. Ils ont été copiés durant le second quart ou vers le milieu du IXe s., et sont signés de QI à QVI, tandis que les ff. 21-40v ont été copiés plus tardivement, durant la seconde moitié du IXe s. ou la première moitié du Xe s. Les ff. 44-45 ont été rajoutés pour compléter une lacune du texte, mentionnée au f. 43v par une main du XIVe s.: "hic deficiunt II° folia". La portion manquante du texte a été recopiée par deux mains différentes, du XVIIe s. Les mss. lat. 18237 et 18238 ont été consultés par Etienne Baluze (1630-1718), bibliothécaire de Colbert et canoniste, pour son édition des Capitularia regum francorum."

Should we await IFN-free regimens to treat HCV genotype 1 treatment-naive patients? A cost-effectiveness analysis (ANRS 95141).

BACKGROUND & AIMS: In treatment-naive patients mono-infected with genotype 1 chronic HCV, treatments with telaprevir/boceprevir (TVR/BOC)-based triple therapy are standard-of-care. However, more efficacious direct-acting antivirals (IFN-based new DAAs) are available and interferon-free (IFN-free) regimens are imminent (2015). METHODS: A mathematical model estimated quality-adjusted life years, cost and incremental cost-effectiveness ratios of (i) IFN-based new DAAs vs. TVR/BOC-based triple therapy; and (ii) IFN-based new DAAs initiation strategies, given that IFN-free regimens are imminent. The sustained virological response in F3-4/F0-2 was 71/89% with IFN-based new DAAs, 85/95% with IFN-free regimens, vs. 64/80% with TVR/BOC-based triple therapy. Serious adverse events leading to discontinuation were taken as: 0-0.6% with IFN-based new DAAs, 0% with IFN-free regimens, vs. 1-10% with TVR/BOC-based triple therapy. Costs were euro60,000 for 12weeks of IFN-based new DAAs and two times higher for IFN-free regimens. RESULTS: Treatment with IFN-based new DAAs when fibrosis stage ⩾F2 is cost-effective compared to TVR/BOC-based triple therapy (euro37,900/QALY gained), but not at F0-1 (euro103,500/QALY gained). Awaiting the IFN-free regimens is more effective, except in F4 patients, but not cost-effective compared to IFN-based new DAAs. If we decrease the cost of IFN-free regimens close to that of IFN-based new DAAs, then awaiting the IFN-free regimen becomes cost-effective. CONCLUSIONS: Treatment with IFN-based new DAAs at stage ⩾F2 is both effective and cost-effective compared to TVR/BOC triple therapy. Awaiting IFN-free regimens and then treating regardless of fibrosis is more efficacious, except in F4 patients; however, the cost-effectiveness of this strategy is highly dependent on its cost.

Potencial reprodutivo de Chrysoperla externa (Hagen) (Neuroptera, Chrysopidae) em função do número de indivíduos por unidade de criação

Verificou-se o efeito de diferentes densidades de insetos por unidade de criação sobre o potencial reprodutivo de Chrysoperla externa. Utilizaram-se adultos da geração F4 mantidos a 25 ± 1ºC, 70 ± 10% de UR e fotofase de 12 horas. Foram utilizadas as seguintes densidades por unidade de criação (10 cm de diâmetro por 23 cm de altura e volume de 1650 cm³): um macho e três fêmeas, dois machos e seis fêmeas, três machos e nove fêmeas e quatro machos e doze fêmeas. Avaliou-se o período de pré-oviposição, a oviposição diária e total por fêmea e por unidade de criação, as porcentagens de ovos viáveis e inférteis e o índice de aproveitamento, calculado por fêmea e por unidade de criação. A densidade quatro machos e doze fêmeas apresentou melhor aproveitamento da unidade de criação, compensando as reduções observadas nos valores de postura média e total por fêmea.

Aspectos biológicos de Chrysoperla raimundoi Freitas & Penny (Neuroptera, Chrysopidae)

Os crisopídeos são importantes predadores e são encontrados em diversos agroecossistemas. A temperatura é um dos fatores determinantes para o desenvolvimento dos insetos, sendo que existe um gradiente de variação aceitável para cada espécie. Portanto, objetivou-se com este estudo verificar a influência de diferentes temperaturas sobre o desenvolvimento embrionário e pós-embrionário de C. raimundoi assim como verificar as conseqüências nas diferentes gerações. As fases jovens foram criadas em três ambientes com temperaturas constantes de 19,0, 25,0 e 31,0ºC e em um ambiente externo sem controle dos fatores abióticos. Foram observados a duração do período embrionário, do primeiro, segundo e terceiro ínstares, a duração do período larval, pupal e ovo-adulto, assim como, a sobrevivência em cada estágio, estádio e a porcentagem de emergência. O desenvolvimento embrionário e pós-embrionário diferiu entre as gerações F2 e F4. Quanto à influência de diferentes temperaturas para a geração F2, os indivíduos criados a 31,0ºC demonstraram redução na taxa de desenvolvimento com relação aos outros dois ambientes. Para a geração F4, observou-se que as diferentes temperaturas influenciaram no desenvolvimento, sendo que a 19,0ºC houve prolongamento do mesmo.

Krypton laser photocoagulation induces retinal vascular remodeling rather than choroidal neovascularization.

The purpose of this study is to analyze the retina and choroid response following krypton laser photocoagulation. Ninety-two C57BL6/Sev129 and 32 C57BL/6J, 5-6-week-old mice received one single krypton (630 nm) laser lesion: 50 microm, 0.05 s, 400 mW. On the following day, every day thereafter for 1 week and every 2-3 days for the following 3 weeks, serial sections throughout the lesion were systematically collected and studied. Immunohistology using specific markers or antibodies for glial fibrillary acidic protein (GFAP) (astrocytes, glia and Muller's cells), von Willebrand (vW) (vascular endothelial cells), TUNEL (cells undergoing caspase dependent apoptosis), PCNA (proliferating cell nuclear antigen) p36, CD4 and F4/80 (infiltrating inflammatory and T cells), DAPI (cell nuclei) and routine histology were carried out. Laser confocal microscopy was also performed on flat mounts. Temporal and spatial observations of the created photocoagulation lesions demonstrate that, after a few hours, activated glial cells within the retinal path of the laser beam express GFAP. After 48 h, GFAP-positive staining was also detected within the choroid lesion center. "Movement" of this GFAP-positive expression towards the lasered choroid was preceded by a well-demarcated and localized apoptosis of the retina outer nuclear layer cells within the laser beam path. Later, death of retinal outer nuclear cells and layer thinning at this site was followed by evagination of the inner nuclear retinal layer. Funneling of the entire inner nuclear and the thinned outer nuclear layers into the choroid lesion center was accompanied by "dragging" of the retinal capillaries. Thus, from days 10 to 14 after krypton laser photocoagulation onward, well-formed blood capillaries (of retinal origin) were observed within the lesion. Only a few of the vW-positive capillary endothelial cells stained also for PCNA p36. In the choroid, dilatation of the vascular bed occurred at the vicinity of the photocoagulation site and around it. Confocal microscopy demonstrates that the vessels throughout the path lesion are located within the neuroretina while in the choroid (after separation of the neural retina) only GFAP-positive but no lectin-positive cells can be seen. The involvement of infiltrating inflammatory cells in these remodeling and healing processes remained minimal throughout the study period. During the 4 weeks following krypton laser photocoagulation in the mouse eye, processes of wound healing and remodeling appear to be driven by cells (and vessels) originating from the retina.

Frações oxidáveis do carbono orgânico em argissolo vermelho-amarelo sob sistema de aleias

O aporte de matéria orgânica ao solo via leguminosas em sistemas de aleias pode ser uma alternativa para o uso sustentável do trópico úmido. O objetivo deste trabalho foi comparar o aporte de matéria orgânica facilmente oxidável proveniente da combinação de resíduos de diferentes leguminosas utilizadas em sistemas de condução de culturas em aleias sob Argissolo Vermelho-Amarelo. Foram avaliadas duas espécies de leguminosas de alta qualidade de resíduos - leucena (Leucaena leucocephala) e guandu (Cajanus cajan), e duas espécies de baixa qualidade de resíduos - sombreiro (Clitoria fairchildiana) e acácia (Acacia mangium), combinadas entre si, nos seguintes tratamentos: sombreiro + guandu; leucena + guandu; acácia + guandu; sombreiro + leucena; leucena + acácia e testemunha sem leguminosa. As amostras de solo foram coletadas nas profundidades de 0-5 e 5-10 cm, nas entrelinhas. Foi quantificado e fracionado o C orgânico total (COT), estratificado em quatro frações (F1, F2, F3 e F4) com graus decrescentes de oxidação. As áreas com sombreiro/leucena, acácia/leucena e acácia/guandu apresentaram os maiores teores de COT (0-5 cm), e a área testemunha, os menores (5-10 cm). A maior proporção do COT estava nas frações F1+F2; a área testemunha teve os menores teores de C nessas frações. O tratamento acácia/guandu apresentou maiores teores de C na fração F1 nas duas profundidades. O tratamento leucena/guandu apresentou as maiores proporções do COT nas frações F3 + F4. Os resultados indicam que, no cultivo em sistema de aleias, a combinação de leguminosas de alta e baixa qualidade de resíduos (acácia/guandu) favorece o aumento de matéria orgânica facilmente decomponível, enquanto o uso de leguminosas de alta qualidade de resíduos favorece maiores proporções de C somente nas frações mais resistentes (F3 + F4).

Geoquímica de radionuclídeos naturais em solos de áreas circunvizinhas a uma Unidade de Mineração e Atividade de Urânio

Os impactos ambientais advindos da exploração e do beneficiamento de U são, em grande parte, idênticos àqueles causados por atividades minero-extrativistas em geral. Este trabalho teve o objetivo de determinar a partição geoquímica dos radionuclídeos naturais 238U, 226Ra e 210Pb em áreas circunvizinhas à Unidade de Mineração e Atividade de Urânio (URA) das Indústrias Nucleares do Brasil S.A., localizada na Província Uranífera de Lagoa Real, no município de Caetité, na região sudoeste do Estado da Bahia. Foram coletadas amostras de solo em cinco áreas circunvizinhas à URA, representando as principais classes de solos da região, na profundidade de 0-20 cm. Nas cinco áreas, foram determinados o teor de atividade total e o fracionamento geoquímico nas frações: F1 - levemente ácida, F2 - reduzível, F3 - oxidável, F4 - alcalina e F5 - residual. As atividades totais médias foram, em Bq kg-1 de solo, de 50 para 238U, 51 para 226Ra e 159 para 210Pb. Os extraídos na fase potencialmente biodisponível (F1) foram: 11 % para 238U, 13 % para 226Ra e 3 % para 210Pb. O 238U apresentou maior biodisponibilidade nos solos mais ácidos e maior afinidade pelos óxidos de Fe, o que não ocorreu para o 226Ra, tendo este apresentado a maior biodisponibilidade. O 210Pb apresentouse predominantemente associado a F5. As percentagens elevadas de 238U, 226Ra e 210Pb na fração geoquímica F5 indicam que as atividades observadas nos cinco solos estão, predominantemente, associadas ao material que deu origem a esses solos, e não a um processo de contaminação artificial em função da atividade da URA.

Microbiological properties and oxidizable organic carbon fractions of an oxisol under coffee with split phosphorus applications and irrigation regimes

Phosphorus fertilization and irrigation increase coffee production, but little is known about the effect of these practices on soil organic matter and soil microbiota in the Cerrado. The objective of this study was to evaluate the microbiological and oxidizable organic carbon fractions of a dystrophic Red Latossol under coffee and split phosphorus (P) applications and different irrigation regimes. The experiment was arranged in a randomized block design in a 3 x 2 factorial design with three split P applications (P1: 300 kg ha-1 P2O5, recommended for the crop year, of which two thirds were applied in September and the third part in December; P2: 600 kg ha-1 P2O5, applied at planting and then every two years, and P3: 1,800 kg ha-1 P2O5, the requirement for six years, applied at once at planting), two irrigation regimes (rainfed and year-round irrigation), with three replications. The layers 0-5 and 5-10 cm were sampled to determine microbial biomass carbon (MBC), basal respiration (BR), enzyme activity of acid phosphatase, the oxidizable organic carbon fractions (F1, F2, F3, and F4), and total organic carbon (TOC). The irrigation regimes increased the levels of MBC, microbial activity and acid phosphatase, TOC and oxidizable fractions of soil organic matter under coffee. In general, the form of dividing P had little influence on the soil microbial properties and OC. Only P3 under irrigation increased the levels of MBC and acid phosphatase activity.

Frações oxidáveis do carbono orgânico total e macrofauna edáfica em sistema de integração lavoura-pecuária

O crescente nível de degradação das terras tem promovido a adoção de manejos agrícolas que busque aliar a produção agropecuária à conservação do solo. Entre esses, a prática da Integração Lavoura-Pecuária (ILP) tem intensificado-se no Centro-Oeste brasileiro. Com o objetivo de avaliar o efeito em longo prazo do sistema ILP e da sazonalidade, sob a comunidade da macrofauna edáfica e das frações oxidáveis do carbono orgânico total (COT) em áreas de cultivo e Cerradão, foi desenvolvido na Fazenda Cabeceira no município de Maracaju, MS, um estudo em que se mensurou a influência da ILP sobre as frações oxidáveis do COT e sobre a macrofauna edáfica. O sistema ILP está sendo utilizado nessa área desde 2003; o solo foi identificado como Latossolo Vermelho, localizado em área de relevo plano. As áreas amostradas possuem o seguinte histórico: soja/milho + braquiária/algodão/ aveia + pastagem/soja/formação da pastagem/pastagem; as amostragens foram realizadas na época seca, em que as culturas presentes eram pasto, milho+braquiária e algodão; e na chuvosa, com milho+braquiária, algodão e soja. Assim, as áreas nas duas épocas de avaliação foram: pasto/milho, milho+braquiária/ algodão, algodão/soja e uma área nativa de Cerradão. A amostragem foi realizada nas profundidades de 0-10, 10-20 e 20-30 cm, sendo feitas as seguintes determinações: análise da macrofauna edáfica, fracionamento granulométrico da matéria orgânica do solo (MOS) e frações oxidáveis do COT. As áreas não apresentavam delineamento experimental, sendo este um estudo de observação. Os dados foram comparados pelo teste de Kruskal Wallis a 5 % e por meio da análise de redundância. A compartimentalização da MOS pode ser utilizada para a avaliação da qualidade do manejo, sendo os compartimentos mais sensíveis as frações F1 e F2 de frações oxidáveis, pois são mais lábeis no solo, já as frações F3 e F4 são as mais recalcitrantes. Isoptera (cupim) pode estar atuando como agente humificador da matéria orgânica na área de Cerradão, contribuindo para maiores teores de F3 e F4, em relação à F1 e F2 na época seca. Esse padrão somente foi verificado na área de Cerradão, visto que nas áreas de produção, Isoptera é controlado pelo manejo. A falta desse inseto no sistema ILP pode estar reduzindo a estabilização da MOS nas frações F3 e F4.

Genetic evidence for a role of adiponutrin in the metabolism of apolipoprotein B-containing lipoproteins.

Adiponutrin (PNPLA3) is a predominantly liver-expressed transmembrane protein with phospholipase activity that is regulated by fasting and feeding. Recent genome-wide association studies identified PNPLA3 to be associated with hepatic fat content and liver function, thus pointing to a possible involvement in the hepatic lipoprotein metabolism. The aim of this study was to examine the association between two common variants in the adiponutrin gene and parameters of lipoprotein metabolism in 23,274 participants from eight independent West-Eurasian study populations including six population-based studies [Bruneck (n = 800), KORA S3/F3 (n = 1644), KORA S4/F4 (n = 1814), CoLaus (n = 5435), SHIP (n = 4012), Rotterdam (n = 5967)], the SAPHIR Study as a healthy working population (n = 1738) and the Utah Obesity Case-Control Study including a group of 1037 severely obese individuals (average BMI 46 kg/m2) and 827 controls from the same geographical region of Utah. We observed a strong additive association of a common non-synonymous variant within adiponutrin (rs738409) with age-, gender-, and alanine-aminotransferase-adjusted lipoprotein concentrations: each copy of the minor allele decreased levels of total cholesterol on average by 2.43 mg/dl (P = 8.87 x 10(-7)), non-HDL cholesterol levels by 2.35 mg/dl (P = 2.27 x 10(-6)) and LDL cholesterol levels by 1.48 mg/dl (P = 7.99 x 10(-4)). These associations remained significant after correction for multiple testing. We did not observe clear evidence for associations with HDL cholesterol or triglyceride concentrations. In conclusion, our study suggests that adiponutrin is involved in the metabolism of apoB-containing lipoproteins.

Effects of fructose and glucose overfeeding on hepatic insulin sensitivity and intrahepatic lipids in healthy humans.

OBJECTIVE: To assess how intrahepatic fat and insulin resistance relate to daily fructose and energy intake during short-term overfeeding in healthy subjects. DESIGN AND METHODS: The analysis of the data collected in several studies in which fasting hepatic glucose production (HGP), hepatic insulin sensitivity index (HISI), and intrahepatocellular lipids (IHCL) had been measured after both 6-7 days on a weight-maintenance diet (control, C; n = 55) and 6-7 days of overfeeding with 1.5 (F1.5, n = 7), 3 (F3, n = 17), or 4 g fructose/kg/day (F4, n = 10), with 3 g glucose/kg/day (G3, n = 11), or with 30% excess energy as saturated fat (fat30%, n = 10). RESULTS: F3, F4, G3, and fat30% all significantly increased IHCL, respectively by 113 ± 86, 102 ± 115, 59 ± 92, and 90 ± 74% as compared to C (all P < 0.05). F4 and G3 increased HGP by 16 ± 10 and 8 ± 11% (both P < 0.05), and F3 and F4 significantly decreased HISI by 20 ± 22 and 19 ± 14% (both P < 0.01). In contrast, there was no significant effect of fat30% on HGP or HISI. CONCLUSIONS: Short-term overfeeding with fructose or glucose decreases hepatic insulin sensitivity and increases hepatic fat content. This indicates short-term regulation of hepatic glucose metabolism by simple carbohydrates.

Freqüência de irrigação em meloeiro cultivado em solo arenoso

O objetivo deste trabalho foi avaliar o efeito de cinco freqüências de irrigação na produtividade e na eficiência do uso da água em meloeiro cultivado sob fertirrigação por gotejamento em solo arenoso de Tabuleiro Costeiro do Piauí. O delineamento experimental foi em blocos ao acaso, com cinco tratamentos e seis repetições. Os tratamentos foram: F1, F2, F3, F4 e F5, correspondentes às freqüências de irrigação de 0,5, 1, 2, 3 e 4 dias, respectivamente. A freqüência de irrigação influenciou as produtividades comercial e total do meloeiro. As maiores produtividades totais (70,73 t ha-1; 77,99 t ha-1 e 64,21 t ha-1) e comerciais (67,20 t ha-1; 63,88 t ha-1 e 53,67 t ha-1) foram obtidas com as freqüências de 0,5 e de 1 dia, respectivamente. Com aplicações menos freqüentes, houve redução significativa (P<0,01) nas produtividades comercial e total do meloeiro. O peso médio de frutos não foi influenciado pelas freqüências de aplicação de água. A maior e a menor eficiência de uso de água, 24,40 kg m-3 e 14,14 kg m-3, foram obtidas com F1 e F5, respectivamente. As freqüências de irrigação de duas vezes por dia, diária e a cada dois dias, são as recomendadas para o meloeiro cultivado em solo arenoso sob fertirrigação por gotejamento. A eficiência de uso da água no meloeiro é maior quando as freqüências de irrigação são maiores.

Grain yield and seed quality of soybean selected for high protein content

The objective of this work was to evaluate the effects of selection for high protein on seed physiological quality and grain yield of soybean. Four populations of BC1F4 and four of F4, each from a cross between a commercial variety and a line bearing high protein seeds, were used. The high protein content selection has a tendency to affect negatively the seed physiological quality. Estimates of correlation coefficients between protein content and grain yield were mostly negative but varied among populations. It is possible to obtain lines with high protein content, keeping the grain yield and the seed physiological quality of their respective recurrent progenitors.

Influence of triamcinolone intravitreal injection on retinochoroidal healing processes.

To analyze the effects of triamcinolone intravitreal injection on the wound healing processes after argon laser retinal photocoagulation, wild type C57BL/6J mice, 8-12 weeks old underwent a standard argon laser photocoagulation protocol. After pentobarbital anesthesia and pupil dilatation, argon laser lesions were induced (50microm, 400mW, 0.05s). Two photocoagulation impacts created two disc diameters from the optic nerve in both eyes. The photocoagulated mice were divided into four groups: Group I (n=12), photocoagulation controls, did not receive any intravitreous injection. Group II (n=12), received an intravitreous injection of 1microl of balanced salt solution (BSS). Group III (n=12), received an intravitreous injection of 1microl containing 15microg of triamcinolone acetonide (TAAC) in BSS. Two mice from each of these three groups were sacrificed at 1, 3, 7, 14 days and 2 and 4 months after photocoagulation. Group IV (n=10) received 1.5, 3, 7.5, 15, or 30microg of TAAC and were all sacrificed on day 14. The enucleated eyes were subjected to systematic analysis of the cellular remodeling processes taking place within the laser lesion and its vicinity. To this purpose, specific antibodies against GFAP, von Willebrand factor, F4/80 and KI67 were used for the detection of astrocytes, activated Müller cells, vascular endothelial cells, infiltrating inflammatory cells and actively proliferating cells. TUNEL reaction was also carried out along with nuclear DAPI staining. Temporal and spatial observations of the created photocoagulation lesions demonstrate that 24h following the argon laser beam, a localized and well-delineated affection of the RPE cells and choroid is observed in mice in Groups I and II. The inner retinal layers in these mice eyes are preserved while TUNEL positive (apoptotic) cells are observed at the retinal outer nuclear layer level. At this stage, intense staining with GFAP is associated with activated retinal astrocytes and Müller cells throughout the laser path. From day 3 after photocoagulation, dilated new choroidal capillaries are detected on the edges of the laser lesion. These processes are accompanied by infiltration of inflammatory cells and the presence of proliferating cells within the lesion site. Mice in Group III treated with 15microg/mul of triamcinolone showed a decreased number of infiltrating inflammatory cells and proliferating cells, which was not statistically significant compared to uninjected laser treated controls. The development of new choroidal capillaries on the edges of the laser lesion was also inhibited during the first 2 months after photocoagulation. However, on month 4 the growth of new vessels was observed in these mice treated with TAAC. Mice of Group IV did not show any development of new capillaries even with small doses. After argon laser photocoagulation of the mouse eye, intravitreal injection of triamcinolone markedly influenced the retina and choroid remodeling and healing processes. Triamcinolone is a powerful inhibitor of the formation of neovessels in this model. However, this inhibition is transient. These observations should provide a practical insight for the mode of TAAC use in patients with wet AMD.

Intravitreous injection of PLGA microspheres encapsulating GDNF promotes the survival of photoreceptors in the rd1/rd1 mouse.

PURPOSE: To evaluate the potential delay of the retinal degeneration in rd1/rd1 mice using recombinant human glial cell line-derived neurotrophic factor (rhGDNF) encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) microspheres. METHODS: rhGDNF-loaded PLGA microspheres were prepared using a water in oil in water (w/o/w) emulsion solvent extraction-evaporation process. In vitro, the rhGDNF release profile was assessed using radiolabeled factor. In vivo, rhGDNF microspheres, blank microspheres, or microspheres loaded with inactivated rhGDNF were injected into the vitreous of rd1/rd1 mice at postnatal day 11 (PN11). The extent of retinal degeneration was examined at PN28 using rhodopsin immunohistochemistry on whole flat-mount retinas, outer nuclear layer (ONL) cell counting on histology sections, and electroretinogram tracings. Immunohistochemical reactions for glial fibrillary acidic protein (GFAP), F4/80, and rhodopsin were performed on cryosections. RESULTS: Significant delay of rod photoreceptors degeneration was observed in mice receiving the rhGDNF-loaded microspheres compared to either untreated mice or to mice receiving blank or inactivated rhGDNF microspheres. The degeneration delay in the eyes receiving the rhGDNF microspheres was illustrated by the increased rhodopsin positive signals, the preservation of significantly higher number of cell nuclei within the ONL, and significant b-wave increase. A reduction of the subretinal glial proliferation was also observed in these treated eyes. No significant intraocular inflammatory reaction was observed after the intravitreous injection of the various microspheres. CONCLUSIONS: A single intravitreous injection of rhGDNF-loaded microspheres slows the retinal degeneration processes in rd1/rd1 mice. The use of injectable, biodegradable polymeric systems in the vitreous enables the efficient delivery of therapeutic proteins for the treatment of retinal diseases.