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INIBIBB 05455

INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BAHIA BLANCA

Unidad Ejecutora - UE

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Título:

"Involvement of Müller glial cells in photoreceptor replacement, en el Simposio sobre:"Molecular mechanisms involved in retinal regeneration and differentiation",

Autor/es:

POLITI L., SIMON V., AND ROSTEIN N

Lugar:

BUZIOS , BRASIL

Reunión:

Simposio; PRIMER REUNION NEUROLATAM; 2008

Institución organizadora:

Simposio sobre:"Molecular mechanisms involved in retinal regeneration and differentiation

Resumen:

INVOLVEMENT OF MÜLLER GLIAL CELLS IN PHOTORECEPTOR REPLACEMENT L. Politi, V. Simón and N. Rotstein. Instituto de Investigaciones Bioquímicas (INIBIBB) and Universidad Nacional del Sur. Bahía Blanca, Argentina The loss of photoreceptors (PHRs) is the main cause of blindness in retinitis pigmentosa and several neurodegenerative retinal diseases for which there is still no cure. Since Müller cells display stem cell properties, they are potential candidates for PHR replacement; however, their use requires establishing how to regulate their cell cycle and promote their differentiation as PHRs. To investigate the molecular and cellular factors that regulate these processes we have used cultures of pure retinal neurons or co-cultures of retinal neurons and Müller cells obtained from newborn rats. Secondary and tertiary cultures prepared from these co-cultures were incubated in media with or without serum, supplemented or not with insulin or docosahexaenoic acid (DHA), a lipid molecule that promotes PHR survival and differentiation. After different time periods, cells were fixed and cell cycle progression and differentiation as neurons and PHRs were investigated. In the absence of Müller cells, a significant number of neuroblasts (NBs) took up bromodeoxiuridine (BrdU) and expressed the stem cell marker nestin and Pax6, required for eye development, during the first two days in vitro. Then, these cells stopped dividing and differentiated as retinal neurons, and NBs were no longer observed; neither in primary nor in secondary cultures. On the contrary, with serum-containing media, NBs were found in primary, secondary and tertiary neuroglial co-cultures, many of which took up BrdU. Noteworthy, 4 days later a small fraction of these cells expressed neuronal markers such as Neu-N and PHR markers, like Crx, Rho4D2 and a PHR-specific transcription factor. These results suggest that Müller cells might preserve the survival and/or promote the proliferation of NBs and these progenitors might acquire a PHR fate as a default differentiation pattern. When secondary cultures were incubated in serum-free media, with insulin and DHA, about 50% of NBs rapidly developed long axons and a characteristic PHR phenotype, suggesting that DHA might speed up their differentiation as PHRs. In conclusion, Müller cells might preserve and/or promote the generation of neuronal progenitors, which would eventually acquire a PHR fate and specific molecular cues, such as insulin or DHA might stimulate these progenitors to achieve this PHR phenotype. (Supported by CONICET, FONCYT and UNS)