Vision is totally dependent on the ability of the retina to receive images from outside the eye, convert the information through photochemical and biochemical reactions into electrical signals, and transmit these signals to the visual cortex in the brain via the optic nerve. Consequently, the retina is an extremely complex tissue composed of ten different layers of cells that process the visual information and send it on to the brain. Defects and/or malfunctions in the physiology of these cells have a significant effect on vision. The major retinal diseases stem from either genetic defects or diabetes (and other systemic diseases) or are related to the normal or abnormal aging process such as AMD.
22.214.171.124 Drugs to Treat Diabetic Retinopathy and Angiogenesis
Diabetic retinopathy (DR) occurs in 27% of diabetics after 5-10 years of contracting diabetes and up to 90% have DR after more than 10 years of diabetes. DR essentially stems from retinal ischemia due to thickening of retinal capillary basement membranes when capillary pericytes start to die off. The ensuing ischemia causes the overexpression of VEGF, which in turn causes capillaries to leak and cause edema. VEGF also stimulates the growth of new blood vessels. This neovascularization could be perceived as a compensatory mechanism, but it is actually detrimental, since the new blood vessels disrupt retinal function. Deterioration of vision in DR is due to macular edema and proliferation of fibrovascular membranes that can lead to retinal detachment. Current treatments for DR are limited to laser photocoagulation of the leaky blood vessels, but this unfortunately destroys the underlying and surrounding retinal tissue. A much more specific approach is the use of photodynamic therapy, where a photosensitizing dye is given intravenously followed by ocular laser irradiation. Pharmacotherapy is not currently possible for DR, although a number of agents are in various stages of development.86 These include the protein kinase C-b inhibitor (LY333531; ruboxistaurin mesylate), which blocks the VEGF signaling pathway87; intravitrially administered glucocorticoids (e.g., dexamethasone, trancinolone, and fluocinolone], which are expected to reduce retinal edema and perhaps also curb neovascularization; and nonsteroidal anti-inflammatory agents, such as celecoxib, which may reduce the local inflammation and edema in DR.86 It is possible that the P2Y2 agonist INS37217 may find future utility in DR treatment by promoting fluid absorption away from the edematous sites.73 Angiostatic cortisines, e.g., anecortave acetate, may also prove useful for treating the neovascularization found in DR.88
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