Factors modulating the effect of retinoids on cultured retinal pigment epithelial cell proliferation

Abstract

The effect of several naturally-occurring retinoids and 13-cis-retinoic acid on the proliferation of cultured bovine retinal pigment epithelial (RPE) cells was investigated. None of the retinoids tested were toxic to the cultures and all, except retinylpalmitate, inhibited cell proliferation when given for more than 3 days. The relative potencies of the retinoids were; all-trans-retinoic acid greater than 13-cis-retinoic acid greater than all-trans-retinol approximately equal to all-trans-retinaldehyde. Uptake of retinoic acid by cultured RPE cells was 10-fold less than the uptake of retinol. Although retinoic acid-treated cultures showed strong density-dependent growth inhibition, cellular proliferation was inhibited more in sparse cultures than in dense ones. Retinoic acid did not significantly inhibit the proliferation of first passage bovine or rabbit RPE cells, but partially inhibited the proliferation of first passage human RPE cells. The sensitivity of all these cultures to growth inhibition by retinoic acid increased in subsequent subcultures, yet there was no effect of passage number on retinoic acid uptake. This study demonstrates that RPE cell proliferation can be inhibited by retinoic acid but the sensitivity of these cells to the retinoid's effects are modulated by incubation time, in vitro aging, and cell density.

Effect of Retinoic Acid on Proliferation and Polyamine Metabolism in Cultured Bovine Retinal Pigment Epithelial Cells

“…A previous study demonstrated that RA did not promote proliferation of second-passage bovine RPE cells [16]. The reason for this may be due to the low concentration (1 ÌM) of RA used since we have achieved similar results at this concentration ( fig.…”

“…It has recently been reported that the decreased metabolism of RA in the fourth passage of bovine RPE cultures compared to that in earlier passage cultures may explain their increased sensitivity to growth inhibition by RA [29]. Additionally, it has been reported that a long period of RA incubation, that is more than 7 days of incubation or further culture after confluency, is required to achieve inhibition of RPE growth in vitro [15,16,18].…”

“…They demonstrated that RA caused an increase in baseline [ 3 H]thymidine incorporation and further increased insulin-stimulated [ 3 H]thymidine incorporation during the early period of an incubation, while RA significantly arrested the growth of postconfluent RPE cells. According to Doyle et al [16], RA has no inhibitory effect on early passages of cultured bovine RPE cell proliferation. They further showed that the inhibition of RA-treated cell proliferation occurred only after the fourth passage in bovine RPE cells.…”

“…However, previous reports on the effects of retinoids on RPE cell growth are contradictory. Antiproliferative [15][16][17][18], non-proliferative [19,20] and proliferative effects [21] of retinoids on cultured RPE cells have all been reported. The present study was thus undertaken to examine the effect of all-trans-retinoic acid (RA) on the characteristics and mechanisms of growth of RPE cells, using cultured bovine RPE cells.…”

Prolifération vitréo-rétinienne : traitement préventif

“…L'acide 13-cis-rétinoïque, analogue synthétique de la vitamine A, inhibe la croissance de l'épithélium pigmentaire, réduit la sécrétion de fibronectine, modifie la distribution de la vimentine et des microtubules, et inhibe la contractilité cellulaire [56][57][58]. Chez l'animal, l'acide rétinoïque administré dans l'huile de silicone est efficace préventivement sur la survenue de la PVR [59].…”