Background Muller cells in the mammalian retina normally express low levels of glial fibrillary acidic protein （GFAP）; however, its expression is upregulated in response to the loss of retinal neurons. The change in expression of GFAP is one of the earliest indicators of retinal damage and is correlated with the time course of disease. The aim of this study was to investigate the time course of degeneration and the expression of GFAP in the retina of mer knockout mice. Methods A total of 30 mer knockout mice, aged from 15-20 days to 1 year and 32 age-matched wild type mice as controls were tested. Immunohistochemistry was used to show the expression of GFAP in the central and peripheral retina of mer knockout and control mice at postnatal age of 15 days （P15d）, 20 days （P20d）, 4 weeks （P4w）, 6 weeks （P6w）, 8 weeks （P8w）, 3 months （P3m）, 6 months （P6m） and 1 years （P1y）.Results The expression of GFAP in the central and peripheral retina of wild type mice was limited to the retinal ganglion cell and nerve fiber layers. In the central retina of mer knockout mice, GFAP expression was upregulated at P4w and GFAP immunolabelling penetrates across the entire thickness of the retina at P8w; whereas in the peripheral retina, the GFAP expression was upregulated at P20d and GFAP immunolabelling penetrates the entire retina after P4w. Conclusions Increased expression of GFAP in Muller cells of mer knockout mice occur at P20d in the peripheral retina and P4w in the central retina. GFAP expression in Muller cells appears to be a secondary response to the loss of retinal neurons. Increased expression of GFAP may occur prior to any detectable morphological changes in the retina. This study suggests that the loss of retinal neurons may begin in the early stages of retinitis pigmentosa, prior to the discovery of any morphological changes in the retina.
Background Proneurotrophins such as the precursor of nerve growth factor （proNGF） and the precursor of brain-derived neurotrophic factor （proBDNF） interacted with sortilin and p75NTR to form a complex capable of activating an apoptotic signaling. We found that the expression of p75NTR and sortilin was increased in ischemic retina induced by elevated intraocular pressure （lOP）, but the protein expression changes of proNGF and proBDNF in the same situation were not clear. This study aimed to ascertain the protein expression changes of proNGF and proBDNF in ischemic retina induced by elevated lOP.
Background Glaucoma can cause progressive damage to retinal ganglion cells. These cells can be classified as cells projecting to the superior colliculus and melanopsin-containing retinal ganglion cells, which project to the suprachiasmatic nucleus. This study was to investigate the effects of chronic intraocular pressure elevation on melanopsin-containing retinal ganglion cells in rats. Methods Chronic intraocular pressure elevation was induced in one eye of adult Wistar rats by cauterization of three episcleral veins. Intraocular pressure was measured at different intervals with a rebound tonometer. Superior collicular retinal ganglion cells were retrogradely labeled from the superior colliculus with Fluorogold. Melanopsin-containing retinal ganglion cells were visualized by free-floating immunohistochemistry on whole-mount retinas. The number of labeled superior collicular and melanopsin-containing retinal ganglion cells were counted in the sample areas on flat-mounted retinas. Results Compared with contralateral control eyes, the numbers of both superior collicular and melanopsin-containing retinal ganglion cells were significantly reduced after 12 weeks of experimental intraocular pressure elevation （（2317.41±29.96）/mm^2 vs （1815.82±24.25）/mm^2; （26.20±2.10）/mm^2 vs （20.62±1.52）/mm^2, respectively）. The extent of cell loss of the two types of retinal ganglion cells was similar. However, no morphologic changes were found in melanopsin-containing retinal ganglion cells. Conclusion Both melanopsin-containing and superior collicular retinal ganglion cells were damaged by chronic ocular hypertension, indicating that glaucomatous neural degeneration involves the non-image-forming visual pathway.
WANG Huai-zhouLU Qing-junWANG Ning-liLIU HongZHANG LingZHAN Gui-lin
