FIBROBLAST GROWTH-FACTOR INDUCES PROLIFERATING CELL NUCLEAR ANTIGEN-IMMUNOREACTIVE CELLS IN GOLDFISH RETINA

New rod photoreceptors are added to mature teleost retinas throughout life by regulated proliferation of rod precursor cells (RPCs). In this study, candidate regulators of RPC proliferation, acidic and basic fi broblast growth factors (aFGF and bFGF; 0.1 mu g/eye), interleukin-6 ( IL-6; 0.1 mu g) and phytohaemagglutinin (HA15; 1.0 mu g), were injecte d intravitreally into one eye of goldfish (body length 5-6 cm), and mi totic RPCs in both retinas were detected and counted 3-50 days later b y immunohistochemistry for proliferating cell nuclear antigen (PCNA). Retinal integrity after treatment was assessed by immunohistochemistry for tyrosine hydroxylase (TH) and other retinal antigens. All the age nts applied altered the density of PCNA-immunoreactive (ir) cells in t he outer and inner nuclear layers (ONL and INL) in both retinas as soo n as 2-3 days after unilateral injection. Initially (2-20 days after i njection), particularly in the treated retina, PCNA-ir cells appeared in clusters accompanied by various numbers of scattered individual cel ls, but subsequently the clusters of PCNA-ir cells disappeared while t he density of singly distributed cells increased until 30 days after i njection. At the doses given, these effects were most striking with aF GF and bFGF and less with IL-6 and HA15. In radial cryosections, other cellular elements immunoreactive to markers such as TH, serotonin, ne uropeptide Y, substance P, glutamine synthetase, glial fibrillary acid ic protein and protein kinase C, were found normal in terms of morphol ogy. In addition, a monoclonal antibody (NN-2) was found to label some non-neuronal structures (macrophages, microglia and blood vessels) in side and outside the retina intoxicated with 6-hydroxydopamine, a few NN-2-ir cells being PCNA-positive. However, clustered PCNA-ir and marg inal neuroblast cells were NN-2-negative. These results indicate that FGFs may play an important role in stimulating the proliferation of RP Cs, for example, in the regeneration of fish retinas following neuroti c destruction.