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Whilst several therapeutic strategies are being evaluated in human clinical trials including i.v. delivery of AAV9-based gene therapy, an urgent unmet need is the availability of non-invasive, quantitative measures of neurodegeneration. We hypothesise that as part of the central nervous system, the retina may provide a window through which to \u2018visualise\u2019 degenerative lesions in brain and amelioration of them following treatment. This is reliant on the age of onset and the rate of disease progression being equivalent in retina and brain.\nFor the first time we have assessed in parallel, the nature, age of onset and rate of retinal and brain degeneration in a mouse model of Sanfilippo syndrome. Significant accumulation of heparan sulphate and expansion of the endo\/lysosomal system was observed in both retina and brain pre-symptomatically (by 3\u00a0weeks of age). Robust and early activation of micro- and macroglia was also observed in both tissues. There was substantial thinning of retina and loss of rod and cone photoreceptors by\u2009~\u200912\u00a0weeks of age, a time at which cognitive symptoms are noted. Intravenous delivery of a clinically relevant AAV9-human sulphamidase vector to neonatal mice prevented disease lesion appearance in retina and most areas of brain when assessed 6\u00a0weeks later. Collectively, the findings highlight the previously unrecognised early and significant involvement of retina in the Sanfilippo disease process, lesions that are preventable by neonatal treatment with AAV9-sulphamidase. Critically, our data demonstrate for the first time that the advancement of retinal disease parallels that occurring in brain in Sanfilippo syndrome, thus retina may provide an easily accessible neural tissue via which brain disease development and its amelioration with treatment can be monitored.<\/jats:p>","DOI":"10.1186\/s40478-020-01070-w","type":"journal-article","created":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T17:20:42Z","timestamp":1605633642000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Is the eye a window to the brain in Sanfilippo syndrome?"],"prefix":"10.1186","volume":"8","author":[{"given":"Helen","family":"Beard","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glyn","family":"Chidlow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Neumann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nazzmer","family":"Nazri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meghan","family":"Douglass","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul J.","family":"Trim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marten F.","family":"Snel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert J.","family":"Casson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1038-9884","authenticated-orcid":false,"given":"Kim M.","family":"Hemsley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,11,17]]},"reference":[{"key":"1070_CR1","doi-asserted-by":"publisher","first-page":"204062232090521","DOI":"10.1177\/2040622320905215","volume":"11","author":"MT Almonte","year":"2020","unstructured":"Almonte MT, Capell\u00e0n P, Yap TE, Cordeiro MF (2020) Retinal correlates of psychiatric disorders. 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All breeding, housing and experimental procedures complied with the Australian code for the care and use of animals for scientific purposes (8th edition; 2013) and the Association for Research in Vision and Ophthalmology (ARVO) statement (2016).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable. This manuscript does not contain data from any individual person.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"194"}}