Abstract
Purpose:
The aim of this study is to identify factors leading to loss of rod and cone photoreceptors in RHO P23H transgenic swine
Methods:
Wild-type and P23H transgenic swine eyes were collected at different embryonic and postnatal stages. Eyes from at least three pigs were used for each time point. Retinas were immunostained for apoptosis, and expression of Rhodopsin(cone opsins (Blue and Red/green), Iba-1, TNF-α, MCP-1, and Endoplasmic reticulum (ER) makers (Calnexin, and calreticulin). Cone number was determined by counting successive 100 μm squares along the length of the retina.
Results:
RHO became trapped in the ER at birth in P23H swine, and apoptosis initiated in rods at postnatal day (P1). This rod apoptois coincided with expression of the microglial chemotactic cytokine MCP-1, microglial invasion into the ONL and release of TNF-α. By P3, most blue cones were apoptotic, and by P14 these cones were largely lost. By contrast, red/green cones remained viable until at least P90.
Conclusions:
Light-induced retention of P23H RHO in the ER at birth initiates rod apoptosis in P23H swine. This apoptosis triggers invasion of microglia and release of TNF-α leading to rapid death of blue cones.
Keywords: 696 retinal degenerations: hereditary •
695 retinal degenerations: cell biology •
702 retinitis