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Expression of trkA, trkB, and trkC in Injured and Regenerating Retinal Ganglion Cells of Adult Rats

¹ From the Department of Anatomy, Faculty of Medicine, The University of Hong Kong, China.

PURPOSE. To investigate changes in percentage of tyrosine kinase (trk)A-, trkB-, and trkC-immunopositive (⁺) retinal ganglion cells (RGCs) at various times after optic nerve (ON) axotomy; the proportion of RGCs regenerating axons into peripheral nerve (PN) grafts that are trkA⁺, trkB⁺, and trkC⁺; whether intravitreal PN-ON implants affect trk immunoreactivity; and the levels of trk mRNAs in ON-injured retinas.

METHODS. The ON was transected intraorbitally. Proportions of trkA⁺, trkB⁺, and trkC⁺ RGCs and levels of trk mRNAs were studied by using immunocytochemistry and Northern blot methods, respectively, in injured and RGC-regenerating retinas.

RESULTS. In normal retinas, only small numbers of trkB⁺ and trkC⁺, but not trkA⁺, RGCs were seen. The optic fiber layer was intensively immunolabeled with trkB. After ON injury, the proportions of trkA⁺, trkB⁺, and trkC⁺ RGCs rapidly increased and reached their peaks by 3 to 5 days. During the next 3 weeks, the proportion of trkA⁺ or trkB⁺ RGCs gradually decreased, but the proportion of trkC⁺ RGCs remained high. Intravitreal implants of PN+ON segments transiently but significantly suppressed injury-induced increases in all these trk⁺ RGC proportions for approximately 5 days. In contrast, 3 days after ON injury, quantitative retinal expression of trkA mRNA, and to a lesser extent trkC mRNA, was downregulated, whereas trkB mRNA expression remained unaffected. Higher proportions of trkA⁺ and trkB⁺ RGCs and higher levels of all trk mRNAs were seen in regenerating RGCs and retinas, respectively.

CONCLUSIONS. This study provides a kinetic analysis of expression of trk in RGCs and retinas after ON injury and during regeneration.

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