Purpose: The wide distribution and extensive cell contacts of Müller cells with retinal neurons suggest a variety of functions including secretion of trophic factors that maintain the survival of photoreceptor cells in the normal retina. We have hypothesized that during the early stages of degeneration in the RCS retina, these trophic factors may not be available in concentrations sufficient to maintain photoreceptor cell survival. The effects of Müller cells were, therefore, tested on photoreceptor cells in the early dystrophic retina as well as in retinal expiants. Methods: Fourteen 2-week old RCS rats were injected intravitreally using a dorsal approach with 100,000 Müller cells in 10 (il PBS or PBS alone and sacrificed after 8-10 weeks. The number of layers of photoreceptor cells in the outer nuclear layer (ONL) of paraffin-embedded retinas was then counted to determine the effects of Müller cell injections. Conditioned medium was also collected from Müller cell cultures (MCCM) in basal medium for 48 hrs. and tested for activity on retinal expiants obtained from PN2 normal rats. Retinal expiants were observed for 2 weeks and compared with control expiants grown in basal medium alone. Photoreceptor cell survival in the expiants was determined using fluorescent probes and colorimetric assays. Results: The ONL in RCS retinas that received PBS alone was 0-1 cell in thickness except at the injection site and in the inferior half of the retina where 1-2 layers of photoreceptor cells were detected. In RCS rats injected with cells, Müller cells had proliferated and occupied the vitreal cavity. The ONL was 2-3 cells thick in the superior half of the retina, however, the inferior half had a 6-8 cell thick ONL. MCCM-treated retinal expiants survived longer and exhibited longer neurites as compared with those in basal medium. Conclusion: Our study shows that Müller cells may promote the survival of injured photoreceptors in the dystrophic rat retina. Furthermore, the growth promoting activity of Müllers cells appears to be due to secreted factors.
|Journal||Investigative Ophthalmology and Visual Science|
|State||Published - 1 Dec 1997|