1. ¹TIGEM, Telethon Institute of Genetics and Medicine, Napoli, Italy
2. ²Department of Ophthalmology, Second University of Napoli, Napoli, Italy
3. ³Department "Scienze e Tecnologie Biomediche," School of Medicine, University of L'Aquila, L'Aquila, Italy
4. ⁴Institute of Neuroscience (CNR), Pisa, Italy

Correspondence: Enrico M Surace, Telethon Institute of Genetics and Medicine, Via Pietro Castellino, 111, 80131 Napoli, Italy. Fax +11 39 081 6132351. E-mail: surace@tigem.it

Received 23 December 2008; Accepted 20 April 2009; Published online 12 May 2009.

Abstract

Oculo-cutaneous albinism type 1 (OCA1) is characterized by congenital hypopigmentation and is due to mutations in the TYROSINASE gene (TYR). In this study, we have characterized the morpho-functional consequences of the lack of tyrosinase activity in the spontaneous null mouse model of OCA1 (Tyr^c-2j). Here, we show that adult Tyr^c-2j mice have several retinal functional anomalies associated with photoreceptor loss. To test whether these anomalies are reversible upon TYR complementation, we performed intraocular administration of an adeno-associated virus (AAV)–based vector, encoding the human TYR gene, in adult Tyr^c-2j mice. This resulted in melanosome biogenesis and ex novo synthesis of melanin in both neuroectodermally derived retinal pigment epithelium (RPE) and in neural crest–derived choroid and iris melanocytes. Ocular melanin accumulation prevented progressive photoreceptor degeneration and resulted in restoration of retinal function. Our results reveal novel properties of pigment cells and show that the developmental anomalies of albino mice are associated with defects occurring in postnatal life, adding novel insights on OCA1 disease pathogenesis. In addition, we provide proof-of-principle of an effective gene-based strategy relevant for future application in albino patients.