Immunolocalization of transforming growth factor-alpha and its receptor in the normal and hyperoxia-exposed neonatal rat retina

Transforming growth factor-alpha (TGF-alpha) is a mitogenic polypeptide for a variety of different cells types including retinal neurons and glial cells. We have examined the temporal and spatial expression of TGF-alpha and its receptor in the normal and hyperoxia-exposed neonatal rat retina to determine if the expression is consistent with a role in retinal development and response to retinal injury. We have used immunohistochemistry to examine TGF-alpha and epidermal growth factor receptor (EGF-R) on postnatal days (1, 5, 10, 14, 18, and 25). To examine TGF-alpha and EGF-R expression after retinal injury we studied the retinas from rats which were exposed to 80% oxygen for 10 days and then recovered in room air. Immunolocalization of type IV collagen was performed to examine the retinal vasculature development after hyperoxia. The pattern of TGF-alpha and EGF-R expression in the neural retina evolved from a diffuse pattern on postnatal day 1 to restricted sites on postnatal day 14. The TGF-alpha immunoreactivity was consistent with localization in Müller cells on postnatal day 14. Both TGF-alpha and EGF-R patterns were altered in the retinas from rats that had been exposed to hyperoxia and recovered in room air for 4 days. The type IV confirmed immunostaining confirmed vaso-obliteration in the deep layer of retinal vessels after hyperoxia. Our findings of altered expression of TGF-alpha and EGF-R during retinal development suggests a biological function for this growth factor, possibly promoting retinal cell proliferation, differentiation, and survival. The altered immunolocalization of TGF-alpha and EGF-R in the hyperoxia-exposed retina suggest that TGF-alpha is likely involved in the retinal response to injury.