A QUANTITATIVE STUDY OF THE LATERAL SPREAD OF MULLER CELL RESPONSES TO RETINAL LESIONS IN THE RABBIT

A wide variety of retinal pathology is associated with an increase in Muller glial cell expression of glial fibrillary acidic protein (GFAP) . In this study the time course and spatial spread of the Muller cell GFAP response following argon laser photocoagulation lesions was exami ned in wholemounted rabbit retina. At 24 hours single focal lesions we re surrounded by GFAP positive Muller cell end feet which declined in density with distance but extended as far as 2-3 mm from the lesion. T he Muller cell reaction reached a maximal spread of 4-5 mm at 14 to 21 days and had started to contract by 30 days, leaving a core of GFAP p ositive processes immediately around the lesion site at 60 days. This zone of spread was much larger than the area of disrupted pigment epit helium. Isodensity plots did not reveal any correlation with the traje ctory of retinal ganglion cell axons. The spread of reaction was more confined for lesions within the visual streak than in the dorsal or ve ntral retinal periphery. Multiple lesions within a focal region of ret ina resulted in a greater density of GFAP reactive end feet with a cor responding greater spread. However, when five to ten lesions were made in a horizontal row, the Muller cells over the entire retina became G FAP immunoreactive. This pan-retinal reaction took several days to spr ead, peaked at 7-14 days, and contracted back to the primary lesion si tes by 2 months. This spread of Muller cell reactivity may be triggere d by the diffusion of substances released by injury or it may be due t o direct cellular communication. The extensive indirect effect on Mull er cells of laser irradiation might be an important component of the c linical effect of laser photocoagulation and indicates a long distance communication mechanism between retinal glia which is poorly understo od. This study also shows the importance of the time at which the Mull er cell response is assessed. (C) 1993 Wiley-Liss, Inc.