Müller cell changes precede vascularization of the pigment epithelium in the dystrophic rat retina

The eye is continuously under oxidative stress due to high metabolic activity and reactive oxygen species generated by daily light exposure. The redox-sensitive protein DJ-1 has proven to be essential in order to protect retina and retinal pigment epithelium (RPE) from oxidative-stress-induced degeneration. Here, we analyzed the specific role of Müller cell DJ-1 in the adult zebrafish retina by re-establishing Müller-cell-specific DJ-1 expression in a DJ-1 knockout retina. Loss of DJ-1 resulted in an age-dependent retinal degeneration, including loss of cells in the ganglion cell layer, retinal thinning, photoreceptor disorganization and RPE cell dysfunction. The degenerative phenotype induced by the absence of DJ-1 was inhibited by solely expressing DJ-1 in Müller cells. The protective effect was dependent upon the cysteine-106 residue of DJ-1, which has been shown to be an oxidative sensor of DJ-1. In a label-free proteomics analysis of isolated retinas, we identified proteins differentially expressed after DJ-1 knockout, but with restored levels after Müller cell DJ-1 re-insertion. Our data show that Müller cell DJ-1 has a major role in protecting the retina from age-dependent oxidative stress.

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Contribution of Müller cells toward the regulation of photoreceptor outer segment assembly

Neuron Glia Biology ◽

10.1017/s1740925x05000049 ◽

2004 ◽

Vol 1 (3) ◽

pp. 291-296 ◽

Cited By ~ 5

Author(s):

XIAOFEI WANG ◽

ALESSANDRO IANNACCONE ◽

MONICA M. JABLONSKI

Keyword(s):

Outer Segment ◽

Cell Function ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Müller Cells ◽

Müller Cell ◽

Muller Cells ◽

Outer Segments ◽

Pigment Epithelium Derived Factor ◽

Muller Cell

The assembly of photoreceptor outer segments into stacked discs is a complicated process, the precise regulation of which remains a mystery. It is known that the integrity of the outer segment is heavily dependent upon surrounding cell types including the retinal pigment epithelium and Müller cells; however the role played by Müller cells within this photoreceptor-specific process has not been fully explored. Using an RPE-deprived but otherwise intact Xenopus laevis eye rudiment preparation, we reveal that Müller cell involvement in outer segment assembly is dependent upon the stimulus provided to the retina. Pigment epithelium-derived factor is able to support proper membrane folding after inhibition of Müller cell metabolism by alpha-aminoadipic acid, while isopropyl beta-D-thiogalactoside, a permissive glycan, requires intact Müller cell function. These results demonstrate that both intrinsic and extrinsic redundant mechanisms exist to support the ability of photoreceptors to properly assemble their outer segments. Our study further suggests that the receptor for pigment epithelium-derived factor resides in photoreceptors themselves while that for permissive glycans is likely localized to Müller cells, which in turn communicate with photoreceptors to promote proper membrane assembly.

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