Müller cells promote photoreceptor cell survival in dystrophic retinas and in retinal explants

Antonio Armando Aviles Rosales, H. J. Sheedlo, J. E. Turner, R. S. Roque

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalInvestigative Ophthalmology and Visual Science
Volume38
Issue number4
StatePublished - 1 Dec 1997

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Photoreceptor Cells
Retina
Cell Survival
Retinal Neurons
Injections
Neurites
Conditioned Culture Medium
Fluorescent Dyes
Paraffin
Cell Culture Techniques

Cite this

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title = "M{\"u}ller cells promote photoreceptor cell survival in dystrophic retinas and in retinal explants",
abstract = "Purpose: The wide distribution and extensive cell contacts of M{\"u}ller 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 M{\"u}ller 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 M{\"u}ller 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 M{\"u}ller cell injections. Conditioned medium was also collected from M{\"u}ller 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, M{\"u}ller 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 M{\"u}ller cells may promote the survival of injured photoreceptors in the dystrophic rat retina. Furthermore, the growth promoting activity of M{\"u}llers cells appears to be due to secreted factors.",
author = "Rosales, {Antonio Armando Aviles} and Sheedlo, {H. J.} and Turner, {J. E.} and Roque, {R. S.}",
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Müller cells promote photoreceptor cell survival in dystrophic retinas and in retinal explants. / Rosales, Antonio Armando Aviles; Sheedlo, H. J.; Turner, J. E.; Roque, R. S.

In: Investigative Ophthalmology and Visual Science, Vol. 38, No. 4, 01.12.1997.

Research output: Contribution to journalArticle

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T1 - Müller cells promote photoreceptor cell survival in dystrophic retinas and in retinal explants

AU - Rosales, Antonio Armando Aviles

AU - Sheedlo, H. J.

AU - Turner, J. E.

AU - Roque, R. S.

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