Endogenous Progenitor Cells May Play a Role in Retinal Recovery as a Result of Glaucomatous Damage

Abstract

Abstract: : Purpose: The major cellular elements of the vertebrate neural retina arise from a pool of multipotent progenitor cells (MPCs) largely in response to local cell-cell interactions in an evolutionary conserved temporal and spatial pattern. Experimental evidence increasingly suggests that the adult CNS contains a complement of MPCs capable of exponential growth, cellular migration to specific target regions, and the generations of mature neuronal and glial progeny. More recently the identification of MPCs in the adult rodent eye has been demonstrated. The purpose of this study was to examine cellular proliferation in the retina in a model of raised IOP. Methods: Raised IOP was induced in the rat by cauterizing three episcleral veins (EVO) to produce chronically elevated IOP. Time course data was obtained at 1 week, 2 weeks, 3 weeks, 1 month, and 2 months. Immunohistochemistry to detect the incorporation of the thymidine analog BrdU into newly synthesized DNA to identify MPCs that have newly entered the S-phase of the cell cycle. Results: Animals subject to EVO had consistently elevated IOP in the operated eye as compared to the non-operated fellow eye which served as control. This elevation was present at all time points assessed. Furthermore, BrdU positive cells were seen as early as two weeks following surgery in the EVO eye. The BrdU positive cells were seen in the ciliary body, retina, and optic nerve. No BrdU staining was seen in the non-operated control eye. Conclusion: These data demonstrate that chronic elevation of IOP results in cellular proliferation following glaucomatous injury. Enhanced neurogenesis in the retina may be a compensatory response to raised IOP and may promote functional recovery in glaucoma. Furthermore, strategies aimed at activating endogenous MPC population may be developed as a therapeutic strategy to improve functional outcome in patients with glaucoma.

Keywords: animal model • regeneration • intraocular pressure