The members of the laboratory group that performed the work described in this manuscript are, from right to left, Zhaohui Wang, Dr. Rouel S. Roque, T.J. Bartosh, Ann-Marie Brun (seated), Dr. Harold J. Sheedlo, and Allison Heath.

Retinal Pigment Epithelium Modulates Photoreceptor Differentiation: A Possible Role in Retinal Stem Cell Niche

The research undertaken in this laboratory focuses on developing photoreceptor cells from immature retinal stem/progenitor cells for ultimate transplantation into diseased retinas. Photoreceptor cells reside in the outer part of the retina that respond to light stimuli by a conformational change of the visual pigment rhodopsin that is imbedded in its cell membrane. Following stimulation of rhodopsin a cascade of molecular events is initiated that is sent to the visual cortex of the cerebrum for interpretation (vision). Two of the most common disorders of the retina that exhibit degeneration of photoreceptor cells in humans are retinitis pigmentosa (RP) and age-related macular degeneration (ARMD). RP is a disease of the photoreceptor cell that leads to blindness, while ARMD is a defect of the retinal pigment epithelium that directly leads to the death of photoreceptor cells. In our recently published research a mouse photoreceptor cell line (called 661W) was tested for its response to growth factors secreted by retinal pigment epithelial (RPE) cells that includes basic fibroblast growth factor (FGF-2). The RPE lies immediately adjacent to the photoreceptor cells in the outer retina and is important in maintaining the integrity of these neurons. Under normal culture conditions, the 661W cells expressed nestin, which is a cell marker for immature stem/progenitor cells, but did not express the visual pigment opsin, a marker for mature photoreceptor cells. However, cells cultured in FGF-2 had a multiple-process morphology similar to neurons, an example is the photoreceptor cell, and expressed opsin. This study showed that a cell line displayed characteristics of immature retinal stem/progenitor cells (nestin), but under the influence of FGF-2 these cells became photoreceptor-like in character (opsin). 661W cells following treatment with FGF-2 will be tested for their therapeutic value in diseased retinas, in particular model systems of RP and ARMD. Harold J. Sheedlo, T.J. Bartosh, Zhaohui Wang, Bhooma Srinivasan, Anne M. Zinkernagel and Rouel S. Roque. RPE-derived factors modulate photoreceptor differentiation: a possible role in the retinal stem cell niche, In Vitro Cellular & Developmental Biology-Animal 43:361-370, 2007.