Rescue of photoreceptors from the damaging effects of constant light by midkine, a retinoic acid-responsive gene product

To evaluate the protective effects of midkine (MK), the product of a retinoic acid-responsive gene, on constant light-induced retinal degeneration in albino Sprague-Dawley rats. Midkine, basic fibroblast growth factor (bFGF), MK plus heparin, or buffer controls were injected intravitreally 2 days before constant light exposure. After 7 days of continuous light exposure, the eyes were perfused with fixative, bisected along the vertical meridian, embedded in paraffin, and sectioned. The degree of retinal light damage was assessed for paraffin-embedded sections by cytologic analysis, by measuring the thickness of the outer nuclear layer (ONL), and by counting the number of macrophages. 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 demonstrated 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 controls. Those injected with bFGF had a 1.5-fold increase in number compared with controls. Midkine has shown strong survival-promoting activity in constant light-induced retinal degeneration, and thus has a high degree of neurotrophic activity in vivo.