Failure to Restore Vision after Optic Nerve Regeneration in Reptiles: Interspecies Variation in Response to Axotomy SARAH A. DUNLOP, 1,2 * LISA B.G. TEE, 1 R. VICTORIA STIRLING, 1 ANDREW L. TAYLOR, 1 PHIL B. RUNHAM, 1 ANDY B. BARBER, 1 GERALD KUCHLING, 1 JENNY RODGER, 1,2 J. DALE ROBERTS, 1 ALAN R. HARVEY, 2,3 AND LYN D. BEAZLEY 1,2 1 School of Animal Biology, The University of Western Australia, Crawley 6009, Australia 2 The Western Australian Institute for Medical Research, The University of Western Australia, Crawley 6009, Australia 3 School of Anatomy & Human Biology, The University of Western Australia, Crawley 6009, Australia ABSTRACT Optic nerve regeneration within the reptiles is variable. In a snake, Viper aspis, and the lizard Gallotia galloti, regeneration is slow, although some retinal ganglion cell (RGC) axons eventually reach the visual centers (Rio et al. [1989] Brain Res 479:151–156; Lang et al. [1998] Glia 23:61–74). By contrast, in a lizard, Ctenophorus ornatus, numerous RGC axons regenerate rapidly to the visual centers, but unless animals are stimulated visually, the regenerated projection lacks topography and animals remain blind via the experimental eye (Beazley et al. [2003] J. Neurotrauma 20:1263–1269). V. aspis, G. galloti, and C. ornatus belong respectively to the Serpentes, Lacertidae, and Agamidae within the Eureptilia, the major modern group of living reptiles comprising the Squamata (snakes, lizards, and geckos) and the Crocodyllia. Here we have extended the findings on Eureptilia to include two geckos (Gekkonidae), Cehyra variegata and Nephrurus stellatus. We also examined a turtle, Chelodina oblonga, the Testudines being the sole surviving representatives of the Parareptilia, the more ancient reptilian group. In all three species, visually elicited behavioral responses were absent throughout regeneration, a result supported electrophysiologically; axonal tracing revealed that only a small proportion of RGC axons crossed the lesion and none entered the contralateral optic tract. RGC axons failed to reach the chiasm in C. oblonga, and in G. variegata, and N. stellatus RGC axons entered the opposite optic nerve; a limited ipsilateral projection was seen in G. variegata. Our results support a heterogeneous response to axotomy within the reptiles, each of which is nevertheless dysfunc- tional. J. Comp. Neurol. 478:292–305, 2004. © 2004 Wiley-Liss, Inc. Indexing terms: visual system; evolution; neurotrauma; repair The projection from the retina to the primary visual centers of the brain is a popular model for the study of regeneration in the central nervous system, and it has been established that the capacity for successful optic nerve regeneration varies across the vertebrates (re- viewed in Beazley 2000; Beazley and Dunlop, 2000). In Anamniotes, such as fish (Osteichthyes), almost 100% of retinal ganglion cells (RGCs) survive; RGC axons regen- erate from their cut ends to the visual centers, the main one being the contralateral optic tectum, by 1–2 months after injury (Murray, 1982; Murray et al., 1982; Schmidt et al., 1983; Hartleib and Steurmer, 1989). Within the Amphibia, a similar pattern is seen except that the num- bers of surviving RGCs is lower compared with fish, rang- ing from 50% to 70% (Litoria moorei: Humphrey and Bea- Grant sponsor: National Health and Medical Research Council (Austra- lia); Grant number: 992319; Grant sponsor: Neurotrauma Research Pro- gram (WA). *Correspondence to: Sarah A. Dunlop, School of Animal Biology, Univer- sity of Western Australia, Nedlands, Western Australia 6009, Australia. E-mail: sarah@cyllene.uwa.edu.au Received 24 December 2003; Revised 6 May 2004; Accepted 29 June 2004 DOI 10.1002/cne.20299 Published online in Wiley InterScience (www.interscience.wiley.com). THE JOURNAL OF COMPARATIVE NEUROLOGY 478:292–305 (2004) © 2004 WILEY-LISS, INC.