Protein delivery for retinal diseases: from basic considerations to clinical applications.

Because the eye is protected by ocular barriers but is also easily accessible, direct intravitreous injections of therapeutic proteins allow for specific and targeted treatment of retinal diseases. Low doses of proteins are required in this confined environment and a long time of residency in the vitreous is expected, making the eye the ideal organ for local proteic therapies. Monthly intravitreous injection of Ranibizumab, an anti-VEGF Fab has become the standard of care for patients presenting wet AMD. It has brought the proof of concept that administering proteins into the physiologically low proteic concentration vitreous can be performed safely. Other antibodies, Fab, peptides and growth factors have been shown to exert beneficial effects on animal models when administered within the therapeutic and safe window. To extend the use of such biomolecules in the ophthalmology practice, optimization of treatment regimens and efficacy is required. Basic knowledge remains to be increased on how different proteins/peptides penetrate into the eye and the ocular tissues, distribute in the vitreous, penetrate into the retinal layers and/or cells, are eliminated from the eye or metabolized. This should serve as a basis for designing novel drug delivery systems. The later should be non-or minimally invasive and should allow for a controlled, scalable and sustained release of the therapeutic proteins in the ocular media. This paper reviews the actual knowledge regarding protein delivery for eye diseases and describes novel non-viral gene therapy technologies particularly adapted for this purpose.

Webster County, Independant Auditor's Reports, Basic Financial and Supplementary Information, Schedule of Findings and Questioned Costs, June 30, 2004

County Audit Report

Iowa Department of Human Services - Case Management Unit, Independent Auditor's Reports, Basic Financial Statements and Supplementary Information, June 30, 2004

State Agency Audit Report

Page County, Independent Auditor's Reports, Basic Financial Statements and Supplementary Information, Schedule of Findings and Questioned Costs, June 30, 2004

County Audit Report

Des Moines County, Independent Auditor's Reports, Basic Financial Statements and Supplementary Information, Schedule of Findings and Questioned Costs, June 30, 2004

County Audit Report

Clinton County, Independent Auditor's Reports, Basic Financial Statements and Supplementary Information, Schedule of Findings and Questioned Costs, June 30, 2004

County Audit Report

Decatur County, Independent Auditor's Reports, Basic Financial Statements and Supplementary Information, Schedule of Findings, June 30, 2004

County Audit Report

Pocahontas County, Independent Auditor's Reports, Basic Financial Statements and Supplementary Information, Schedule of Findings, June 30, 2004

County Audit Report

Madison County, Independent Auditor's Reports, Basic Financial Statements and Supplementary Information, Schedule of Findings, June 30, 2004

County Audit Report

Iowa Communications Network, Independent Auditor's Reports, Basic Financial Statements and Supplementary Information, Schedule of Findings, June 30, 2004

State Agency Audit Report

Mid-Iowa School Improvement Consortium, Independent Auditor's Reports, Basic Financial Statements and Schedule of Findings, June 30, 2004

Other Audit Reports - 28E Organizations

Monona County, Independent Auditor's Reports, Basic Financial Statements and Supplementary Information, Schedule of Findings and Questioned Costs, June 30, 2004

County Audit Report

Black Hawk County, Independent Auditor's Reports, Basic Financial Statements and Supplementary Information, Schedule of Findings and Questioned Costs, June 30, 2004

County Audit Report

Molecular taxonomy of the Formica rufa group (red wood ants) (Hymenoptera: Formicidae): a new cryptic species in the Swiss Alps?

Because of their beneficial impact on forest ecosystems, European red wood ants (Formica rufa group) are protected by law in many European countries and are considered to be among the most reliable bioindicators of forest stability. However, their taxonomy has been much debated and, unfortunately, it is too often neglected. This happens mainly because the morphology-based method for species delimitation requires lots of time and experience. We therefore employed 9 microsatellite loci and mitochondrial DNA (COI gene) to verify the power of genetic markers for red wood ant species delimitation and to investigate the cryptic diversity of these ants within the Eastern Swiss Alps. We analyzed 83 nests belonging to all red wood ant species that occur in the Swiss National Park area. Genetic data indicated that these species represent different genetic pools. Moreover, results showed that Formica aquilonia YARROW, 1955 and F. paralugubris SEIFERT, 1996 often hybridize within the Park, confirming that these two species are genetically very close and could have diverged only recently. Nevertheless, microsatellites also revealed that one entire population, located in the Minger Valley and morphologically identified as F. lugubris ZETTERSTEDT, 1838, is genetically different to all other analyzed F. lugubris populations found within the same area and to other red wood ant species. These findings, confirmed by mitochondrial DNA analyses, suggest the existence of a new cryptic species within the Eastern Swiss Alps. This putative cryptic species has been provisionally named F. lugubris-A2. These results have a great importance for future conservation plans, monitoring and evolutionary studies on these protected ants.

City of Union, Independent Auditor's Reports, Basic Financial Statements and Supplementary Information, Schedule of Findings, June 30, 2004

City Audit Report