Phototransduction in retinal cones: Analysis of parameter importance

In daylight, cone photoreceptors in the retina are responsible for the bulk of visual perception, yet compared to rods, far less is known quantitatively about their biochemistry. This is partly because it is hard to isolate and purify cone proteins. The issue is also complicated by the synergistic i...

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Autores principales:	Colin Klaus, Giovanni Caruso, Vsevolod V. Gurevich, Heidi E. Hamm, Clint L. Makino, Emmanuele DiBenedetto
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a17d3d185c0b4bea99d37b1564483c72
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spelling	oai:doaj.org-article:a17d3d185c0b4bea99d37b1564483c722021-11-04T06:49:32ZPhototransduction in retinal cones: Analysis of parameter importance1932-6203https://doaj.org/article/a17d3d185c0b4bea99d37b1564483c722021-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553137/?tool=EBIhttps://doaj.org/toc/1932-6203In daylight, cone photoreceptors in the retina are responsible for the bulk of visual perception, yet compared to rods, far less is known quantitatively about their biochemistry. This is partly because it is hard to isolate and purify cone proteins. The issue is also complicated by the synergistic interaction of these parameters in producing systems biology outputs, such as photoresponse. Using a 3-D resolved, finite element model of cone outer segments, here we conducted a study of parameter significance using global sensitivity analysis, by Sobol indices, which was contextualized within the uncertainty surrounding these parameters in the available literature. The analysis showed that a subset of the parameters influencing the circulating dark current, such as the turnover rate of cGMP in the dark, may be most influential for variance with experimental flash response, while the shut-off rates of photoexcited rhodopsin and phosphodiesterase also exerted sizable effect. The activation rate of transducin by rhodopsin and the light-induced hydrolysis rate of cGMP exerted measurable effects as well but were estimated as relatively less significant. The results of this study depend on experimental ranges currently described in the literature and should be revised as these become better established. To that end, these findings may be used to prioritize parameters for measurement in future investigations.Colin KlausGiovanni CarusoVsevolod V. GurevichHeidi E. HammClint L. MakinoEmmanuele DiBenedettoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Colin Klaus Giovanni Caruso Vsevolod V. Gurevich Heidi E. Hamm Clint L. Makino Emmanuele DiBenedetto Phototransduction in retinal cones: Analysis of parameter importance
description	In daylight, cone photoreceptors in the retina are responsible for the bulk of visual perception, yet compared to rods, far less is known quantitatively about their biochemistry. This is partly because it is hard to isolate and purify cone proteins. The issue is also complicated by the synergistic interaction of these parameters in producing systems biology outputs, such as photoresponse. Using a 3-D resolved, finite element model of cone outer segments, here we conducted a study of parameter significance using global sensitivity analysis, by Sobol indices, which was contextualized within the uncertainty surrounding these parameters in the available literature. The analysis showed that a subset of the parameters influencing the circulating dark current, such as the turnover rate of cGMP in the dark, may be most influential for variance with experimental flash response, while the shut-off rates of photoexcited rhodopsin and phosphodiesterase also exerted sizable effect. The activation rate of transducin by rhodopsin and the light-induced hydrolysis rate of cGMP exerted measurable effects as well but were estimated as relatively less significant. The results of this study depend on experimental ranges currently described in the literature and should be revised as these become better established. To that end, these findings may be used to prioritize parameters for measurement in future investigations.
format	article
author	Colin Klaus Giovanni Caruso Vsevolod V. Gurevich Heidi E. Hamm Clint L. Makino Emmanuele DiBenedetto
author_facet	Colin Klaus Giovanni Caruso Vsevolod V. Gurevich Heidi E. Hamm Clint L. Makino Emmanuele DiBenedetto
author_sort	Colin Klaus
title	Phototransduction in retinal cones: Analysis of parameter importance
title_short	Phototransduction in retinal cones: Analysis of parameter importance
title_full	Phototransduction in retinal cones: Analysis of parameter importance
title_fullStr	Phototransduction in retinal cones: Analysis of parameter importance
title_full_unstemmed	Phototransduction in retinal cones: Analysis of parameter importance
title_sort	phototransduction in retinal cones: analysis of parameter importance
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/a17d3d185c0b4bea99d37b1564483c72
work_keys_str_mv	AT colinklaus phototransductioninretinalconesanalysisofparameterimportance AT giovannicaruso phototransductioninretinalconesanalysisofparameterimportance AT vsevolodvgurevich phototransductioninretinalconesanalysisofparameterimportance AT heidiehamm phototransductioninretinalconesanalysisofparameterimportance AT clintlmakino phototransductioninretinalconesanalysisofparameterimportance AT emmanueledibenedetto phototransductioninretinalconesanalysisofparameterimportance
_version_	1718445105670520832

Phototransduction in retinal cones: Analysis of parameter importance

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