Progress in Retinal and Eye Research 23 (2004) 475–494 Progress in retinal sheet transplantation Robert B. Aramant a , Magdalene J. Seiler b,c, * a Department of Anatomical Sciences and Neurobiology, University of Louisville, KY, USA b Doheny Eye Institute, Keck School of Medicine, University of Southern California, 1450 San Pablo St., Los Angeles, CA 90033, USA c Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, USA Abstract The aim of retinal transplantation is to prevent blindness and to restore eyesight, i.e. to rescue photoreceptors or to replace damaged photoreceptors with the hope of re-establishing neural circuitry. A promising experimental paradigm is the sub-retinal transplantationofsheetsoffetalretina,withorwithoutitsattachedretinalpigmentepithelium(RPE),intorecipientratswithretinal degeneration. Sheets of fetal retina have already developed their primordial circuitry. Such transplants can develop lamination resembling a normal retina dependent on the presence of healthy RPE either from the host or from the graft. In several retinal degeneration models, transplants have been shown to restore visually evoked responses in an area of the superior colliculus corresponding to the placement of the transplant in the retina. The functional effect of transplants may be due to transplant/host connectivity and/or rescue of host photoreceptors. Insummary,sheetsoffetalretinacanmorphologicallyrepairanareaofadegeneratedretina,andthereisevidencetosuggestthat transplants form synaptic connections with the host and restore visual responses in rats with retinal degeneration. r 2004 Elsevier Ltd. All rights reserved. ARTICLE IN PRESS Contents 1. Introduction ................................................ 476 1.1. Therapies for retinal degeneration .................................. 476 1.2. History of retinal transplantation .................................. 477 1.3. Label of donor tissue for transplantation .............................. 477 1.4. Transplants of stem/progenitor cells ................................. 478 1.5. Transplants of retinal sheets ..................................... 478 2. Retinal degeneration models used for transplantation ........................... 479 2.1. Light damage ............................................. 479 2.2. Inherited models of retinal degeneration ............................... 479 2.2.1. rd mice ............................................ 479 2.2.2. RCS rat—prominent photoreceptor rescue effect by RPE transplants and sham surgery . . 479 2.2.3. Transgenic rodent models .................................. 480 2.2.4. Larger animal models .................................... 480 3. Morphological repair of damaged retinas by fetal retinal sheets ...................... 480 3.1. Introduction ............................................. 480 3.2. Difficulties/requirements ....................................... 480 4. Transplantation of sheets of retina together with its RPE—a necessary and unmatched approach .... 481 4.1. Why cografts? ............................................ 481 4.2. Difficulties/requirements ....................................... 481 4.3. Cografts of human fetal retina with RPE .............................. 481 *Corresponding author. Doheny Eye Institute, Keck School of Medicine, University of Southern California, 1450 San Pablo St., Los Angeles, CA 90033, USA. Tel.: +1-323-442-6532; fax: +1-323-442-6460. E-mail address: mseiler@doheny.org (M.J. Seiler). 1350-9462/$-see front matter r 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.preteyeres.2004.05.003