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Annika K. Söderpalm, Donald A. Fox, Jan-Olof Karlsson, Theo van Veen; Retinoic Acid Produces Rod Photoreceptor Selective Apoptosis in Developing Mammalian Retina. Invest. Ophthalmol. Vis. Sci. 2000;41(3):937-947.
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purpose. All-trans retinoic acid (ATRA) or 9-cis retinoic
acid (9CRA), added to dissociated developing neural retinal cells,
induces progenitor cells to adopt the rod cell’s fate. Retinoic acid
(RA) also produces apoptotic cell death in developing tissues. The
effects of retinoids on mouse retinal development were examined.
methods. Retinas were explanted on postnatal day (PN)1 and cultured with or
without the retinal pigment epithelium (RPE) attached. Retinas were
cultured for 3 weeks in the absence or presence of 100 or 500 nM ATRA
or 9CRA. Morphologic development and apoptotic cell death were examined
using cell-specific immunocytochemical markers, the TdT-dUTP terminal
nick-end labeling (TUNEL) method, and a caspase assay.
results. Retinal explants, with and without RPE, had similar age-dependent
increases in opsin expression. In contrast, explants with RPE had less
apoptosis during the first week than retinas without RPE. In explants
with RPE, ATRA or 9CRA produced rod-selective apoptotic cell death in
which 20% to 25% were lost by PN7 with no further loss by PN21.
9CRA-treated explants without RPE had a decreased number of apoptotic
cells and a higher number of (rhod)opsin-positive cells at PN3.
conclusions. Factors in RPE appear to regulate rod apoptosis in developing retina.
Retinoids produce rod-selective apoptotic cell death during normal rod
differentiation. In contrast, retinoids accelerate the expression of
opsin in retinas without RPE. These differential effects of RA on rod
photoreceptors—apoptosis and differentiation—are similar to those
observed in other developing tissues and play an important role in both
normal and pathologic development.
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