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S.L. Ball, B.W. Hanzlicek; Activation of Muller Cells Revealed by Fos Expression During Early Stages of Photoreceptor Degeneration . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1690.
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Purpose: We have previously used immunohistochemistry to identify light induced Fos expression in amacrine cells of normal mice (Hanzlicek et al., 2004). We now apply this technique to the rds/rds mouse and Royal College of Surgeons (RCS) rat retina to assess the functional potential of the inner retina during and after photoreceptor loss. Methods: At 2 and 9 months of age (during and after photoreceptor degeneration) a light stimulus flickering at 2 Hz was presented to individual rds/rds mice and RCS and wild type Long Evans rats in a ganzfeld for a 1 hour time period. Following light exposure, eyecups were collected and fixed for 30–60 minutes in 4% paraformaldehyde. Eyecups were then cryoprotected in 30% sucrose overnight, embedded in OCT and sectioned on a cryostat at 10 µm. Using standard immunohistochemical techniques retinal sections were labeled with a Fos antibody (sc–52). Eyecups were also collected from age similar animals not exposed to light (NL) and these eyes were processed in parallel with light exposed (L) retinas. A subset of retinal sections were double labeled for both Fos and glutamate synthetase (GS) a Muller cell marker. Results: In WT, RCS and rds/rds retinas, amacrine cells were Fos labeled in L retinas but not in NL retinas during early stages of degeneration. In retinas from RCS rats and rds/rds mice but not WT retinas, Fos expression was also found in small patches of 5–8 GS positive Muller cells before photoreceptor degeneration in both L and NL groups. After photoreceptor degeneration, no Fos expression was found in either cell type in L or NL retinas. Conclusions: Muller cells in degenerating retinas exhibit activation of the Fos protein before photoreceptor loss is complete, regardless of light exposure. This activation does not occur uniformly across the retina but is found in isolated patches of Muller cells and is not present in retinas completely devoid of photoreceptors. This suggests a discrete time period and activation pattern in which Muller cells may be reacting to impending photoreceptor loss. Further definition of the nature and timing of reactive events associated with retinal degeneration is a critical element in the development of therapeutic strategies.
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