RESCUE OF PHOTORECEPTORS FROM THE DAMAGING EFFECTS OF CONSTANT LIGHT BY MIDKINE, A RETINOIC ACID-RESPONSIVE GENE-PRODUCT

Purpose. To evaluate the protective effects of midkine (MK), the produ ct of a retinoic acid-responsive gene, on constant light-induced retin al degeneration in albino Sprague-Dawley rats. Methods. Midkine, basic fibroblast growth factor (bFGF), MK plus heparin, or buffer controls were injected intravitreally 2 days before constant light exposure. Af ter 7 days of continuous light exposure, the eyes were perfused with f ixative, bisected along the vertical meridian, embedded in paraffin, a nd sectioned. The degree of retinal light damage was assessed for para ffin-embedded sections by cytologic analysis, by measuring the thickne ss of the outer nuclear layer (ONL), and by counting the number of mac rophages. Results. After 1 week of constant light exposure, uninjected controls and those injected with phosphate-buffered saline (PBS) lost most of the photoreceptor inner and outer segments, and the thickness of the ONL was decreased. Eyes that were injected with MK or bFGF dem onstrated a significant rescue in the photoreceptor layer with a two- to threefold increase in the ONL thickness. The number of macrophages in eyes injected with MK was significantly suppressed compared with co ntrols. Those injected with bFGF had a 1.5-fold increase in number com pared with controls. Conclusions. Midkine has shown strong survival-pr omoting activity in constant light-induced retinal degeneration, and t hus has a high degree of neurotrophic activity in vivo.