Molecular and structural alterations of Muller glial cells from the ?rd? retina

POLITI, L.E.; VOLONTÉ, Y.A.; GERMAN, O. L.; SIMON, V.; ROTSTEIN, N.

San Francisco, California, USA

Congreso; ISER 2014. 21st Biennial Meeting of the International Society for Eye Research; 2014

The molecular bases of retinitis pigmentosa (RP) are well-established; however these diseases have still no treatment. The use of stem cells to regenerate the damaged retinas is being intensely investigated as a promising treatment for RP. Recent work from several laboratories has shown that Muller glial cells (MGC) are stem cells in the eye, which may compensate physiological neuronal loss. In addition, MGC have multiple roles in the eye, providing nutrients and trophic factors essential for photoreceptor survival. Little is known about the involvement of MGC in RP. Using a well-known model of RP, the rd mouse, we here investigated whether in addition to the well-known molecular abnormalities of photoreceptors, MGC also presented structural or molecular changes. To investigate this, we prepared mixed neuro-glial cultures from ?rd? and wild type (wt) mice retinas. Nuclear morphology was substantially altered in rd MGC. By day 21, 93% of MGC nuclei in wt cultures showed round, oval; or irregular shapes and only 7% of them evidenced indentations in their morphology. By contrast, in ?rd? cultures MGC nuclei having deep indentations increased to about 20%. Expression of nestin, a stem cell marker, was markedly reduced from about 80% in MGC in wt cultures to nearly 40% in ?rd? cultures. The filamentous pattern of nestin was usually lost in ?rd? MGC. Noteworthy, while in wt cultures each glial cell supported about 2 photoreceptor progenitors, this number was 3 times higher in ?rd? cultures. MGC ?overload? with photoreceptor progenitors in ?rd? mice might deprive them from essential trophic support and contribute to photoreceptor degeneration. In conclusion, our results suggest that in addition to the alterations in "rd" photoreceptors, changes in structure of MGC and in their interactions with neurons might also be involved in photoreceptor degeneration.