Effect of prenatal isotretinoin on postnatal development of rat retina and expression of doublecortin positive cells: A morphometric and histopathological analysis

Objective: Isotretinoin is a 13-cis-retinoic acid (RA), a vitamin A derivative required for normal development of central nervous system (CNS) including the retina. However it is also known to be a teratogen specially affecting the craniofacial region and frontal cortex neurons. Since neuronal proliferation and apoptotic cell death occur continuously during early postnatal retinal development, we investigated the effect of prenatal isotretinoin on postnatal development of retina. Methods: Pregnant rat received isotretinoin during early or mid-gestational period and the control received an equal volume of vegetable oil instead. The histopathological and morphometric analysis of the retina was performed on postnatal day 7, 14 and 30 using haematoxylin and eosin staining. To evaluate the freshly formed neurons retinal sections were also stained with doublecortin (DCX) on day 14 and day 30. Results: A significant loss of neurons in inner nuclear and ganglionic cell layers was evident in both treatment regimes. The expression of DCX positive cells were confined to the inner nuclear layers in control group as well as in rats treated with isotretinoin during early gestation on postnatal 14. Postnatal day 30 did not showed any DCX positive cells. Conclusion: The present study clearly demonstrates that prenatal isotretinoin reduce the neuronal population in retina apart from usual apoptosis. It also confirms that the formation of new neurons occur more specifically in inner nuclear layer of the retina around second week of postnatal development.