{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T16:03:06Z","timestamp":1782489786621,"version":"3.54.5"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T00:00:00Z","timestamp":1611532800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Frank and Sheri Etscorn","award":["Robert Cormack Memorial Award"],"award-info":[{"award-number":["Robert Cormack Memorial Award"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Pre-clinical testing of retinal pathology and treatment efficacy depends on reliable and valid measures of retinal function. The electroretinogram (ERG) and tests of visual acuity are the ideal standard, but can be unmeasurable while useful vision remains. Non-image-forming responses to light such as the pupillary light reflex (PLR) are attractive surrogates. However, it is not clear how accurately such responses reflect changes in visual capability in specific disease models. The purpose of this study was to test whether measures of non-visual responses to light correlate with previously determined visual function in two photoreceptor degenerations.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>The sensitivity of masking behavior (light induced changes in running wheel activity) and the PLR were measured in 3-month-old wild-type mice (WT) with intact inner retinal circuitry, <jats:italic>Pde6b<\/jats:italic>-<jats:italic>rd1\/rd1<\/jats:italic> mice (<jats:italic>rd1<\/jats:italic>) with early and rapid loss of rods and cones, and <jats:italic>Prph2-Rd2\/Rd2<\/jats:italic> mice (<jats:italic>Rd2<\/jats:italic>) with a slower progressive loss of rods and cones.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>In <jats:italic>rd1<\/jats:italic> mice, negative masking had increased sensitivity, positive masking was absent, and the sensitivity of the PLR was severely reduced. In <jats:italic>Rd2<\/jats:italic> mice, positive masking identified useful vision at higher light levels, but there was a limited decrease in the irradiance sensitivity of negative masking and the PLR, and the amplitude of change for both underestimated the reduction in irradiance sensitivity of image-forming vision.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Together these data show that in a given disease, two responses to light can be affected in opposite ways, and that for a given response to light, the change in the response does not accurately represent the degree of pathology. However, the extent of the deficit in the PLR means that even a limited rescue of rod\/cone function might be measured by increased PLR amplitude. In addition, positive masking has the potential to measure effective treatment in both models by restoring responses or shifting thresholds to lower irradiances.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0244702","type":"journal-article","created":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T18:35:40Z","timestamp":1611599740000},"page":"e0244702","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Pupillary reflex and behavioral masking responses to light as functional measures of retinal degeneration in mice"],"prefix":"10.1371","volume":"16","author":[{"given":"Ethan O.","family":"Contreras","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carley G.","family":"Dearing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crystal A.","family":"Ashinhurst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betty A.","family":"Fish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sajila N.","family":"Hossain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariana M.","family":"Rey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Primal D.","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4317-4572","authenticated-orcid":true,"given":"Stewart","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,1,25]]},"reference":[{"key":"pone.0244702.ref001","article-title":"Gene therapy restores vision-dependent behavior as well as retinal structure and function in a mouse model of RPE65 leber congenital amaurosis","author":"JJ Pang","year":"2006","journal-title":"Mol Ther"},{"key":"pone.0244702.ref002","article-title":"Biology and therapy of inherited retinal degenerative disease: Insights from mouse models","author":"S Veleri","year":"2015","journal-title":"DMM Disease Models and Mechanisms"},{"key":"pone.0244702.ref003","article-title":"Vision in laboratory rodents\u2014Tools to measure it and implications for behavioral research","author":"H Leinonen","year":"2018","journal-title":"Behavioural Brain Research"},{"key":"pone.0244702.ref004","article-title":"Rapid quantification of adult and developing mouse spatial vision using a virtual optomotor system","author":"GT Prusky","year":"2004","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"pone.0244702.ref005","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.1016\/S0042-6989(00)00081-X","article-title":"Behavioral assessment of visual acuity in mice and rats","volume":"40","author":"GT Prusky","year":"2000","journal-title":"Vision Res"},{"key":"pone.0244702.ref006","article-title":"Visual detection, pattern discrimination and visual acuity in 14 strains of mice","author":"AA Wong","year":"2006","journal-title":"Genes, Brain Behav"},{"key":"pone.0244702.ref007","article-title":"Visual function testing: A quantifiable visually guided behavior in mice","author":"S Thompson","year":"2008","journal-title":"Vision Res"},{"key":"pone.0244702.ref008","article-title":"Photoreceptor cells with profound structural deficits can support useful vision in mice","author":"S Thompson","year":"2014","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"pone.0244702.ref009","article-title":"Melanopsin and rod\u2014cone photoreceptive systems account for all major accessory visual functions in mice","author":"S Hattar","year":"2003","journal-title":"Nature"},{"key":"pone.0244702.ref010","article-title":"Chromatic Pupil Responses. 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Crippa S","year":"2018","journal-title":"Front Neurol"},{"key":"pone.0244702.ref045","article-title":"Long-term restoration of rod and cone vision by single dose rAAV-mediated gene transfer to the retina in a canine model of childhood blindness","author":"GM Acland","year":"2005","journal-title":"Mol Ther"},{"key":"pone.0244702.ref046","article-title":"Safety and Efficacy of Gene Transfer for Leber\u2019s Congenital Amaurosis","author":"AM Maguire","year":"2008","journal-title":"N Engl J Med"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0244702","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T18:35:53Z","timestamp":1611599753000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0244702"}},"subtitle":[],"editor":[{"given":"Alfred S.","family":"Lewin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,1,25]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1,25]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0244702","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,25]]}}}