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C. Jiang, X. Zhang, M. Maria, M. Young; Neuroprotection of Retinal Ganglion Cells and Their Axons With Gdnf & Vit E Loaded Biodegradable Microparticles in Rat Experimental Glaucoma Model. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3177.
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© ARVO (1962-2015); The Authors (2016-present)
Glaucoma is an optic neuropathy characterized by degeneration of retinal ganglion cells (RGCs) and their axons resulting in progressive loss of vision. Effective neuroprotection in glaucoma likely requires the consistent availability of the active agent for prolonged periods of time. The purpose of this study was to evaluate the long-term neuroprotection of intravitreal injection of GDNF & Vit E loaded biodegradable microparticles in promoting the survival of RGCs and their axons in a rat experimental glaucoma model.
Chronic elevation of IOP was induced in rats through injection of hypertonic saline into the episcleral veins. IOP was measured twice weekly in awake rats using topical anesthesia. Microparticles loaded with GDNF & Vit E were injected into the vitreous cavity of rats with elevated IOP, with injections of GDNF, Vit E, and blank microparticles serving as controls. Histological analysis was used to quantify surviving RGCs and axons. The levels of GDNF, Caspase 9, and GFAP expression within the retinas of rats with IOP elevation were quantitatively compared by Western blot. TUNEL staining was used to detect apoptosis.
The duration of IOP elevation in this study was 10 weeks. GDNF & Vit E microparticle treatment significantly increased the RGC and axon survival (P < 0.001) compared with GDNF, Vit E, and blank microparticles. IOP elevation resulted in significantly decreased expression of GDNF and increased expression of GFAP within retinas. GDNF & Vit E microparticle treatment significantly increased the expression of GDNF and decreased the expression of GFAP and Caspase 9. Apoptotic cells in ganglion cell layer were significantly decreased in treatment group. In addition, GDNF treatment moderately reduced cupping of the optic nerve head.
Treatment with GDNF & Vit E via biodegradable microparticles significantly increased the survival of RGCs and their axons in this experimental glaucoma model. The enhanced survival of RGCs and their axons is associated with increased expression of GDNF, together with decreased expression of GFAP and Caspase 9.
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