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Mechanisms of intrinsic light responses in the ocular lens

Award Number: R01EY032752
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2021
PERIOD OF PERFORMANCE END DATE: 05/31/2025

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Mechanisms of intrinsic light responses in the ocular lens - We normally think of the neural retina as the only light-responsive tissue of mammals. Recently, however, it has been shown that the atypical opsins Opsin 3 (OPN3, encephalopsin) and Opsin 5 (OPN5, neuropsin) are expressed in other tissues. Investigating this further, the Lang lab has shown that OPN5 mediates light reception in skin and brain and that OPN3 does so in adipose tissue. In all cases, these opsins mediate direct, acute light responsiveness of the non-retinal tissue. Here we identify the ocular lens as an intrinsically light sensitive tissue. Lenses isolated in culture show an acute response to blue (470 nm) light that changes their optical properties. According to preliminary data, OPN3 is required for the intrinsic light response of the lens and we further show that light stimulation of the lens suppresses the phosphorylation of the water channel Aquaporin 0, a substrate of protein kinase A. Since Aquaporin 0 regulates lens transparency, we hypothesize that an OPN3-dependent, intrinsic light response regulates aquaporin activity via the cAMP-PKA pathway and thus the optical performance of the lens. This hypothesis implies that the lens has distinct optical states adapted to daytime and nighttime vision. Seeking a deeper understanding of this unique lens biology, we propose three aims, (Aim 1), To determine which G-protein OPN3 uses for signaling in the lens, (Aim 2), To confirm the OPN3 signaling mechanism, and the influence of that signaling on aquaporins and lens transparency including cataractogenesis, and (Aim 3), To assess the influence of lens OPN3 on lens refractive power and eye refractive development. This application builds on a long history of interest in the ocular lens from the Lang lab and combines expertise in lens cell biology from Steve Bassnett and eye refractive development from Rafael Grytz and Machelle Pardue. Identification of a direct, light- and opsin-dependent optical change in the ocular lens is unexpected and so when complete, this work will fundamentally change the way we think of the eye as a light sensing organ. There is also the possibility that this work will identify the lens as a new target for myopia treatment.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = -$6 )
2026	2024	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Vision Research	000	4	1/6/2026	NON-COMPETING CONTINUATION	-$6
														Subtotal = -$6

Issue Date FY: 2024 ( Subtotal = $382,724 )
2024	2024	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Vision Research	000	4	6/14/2024	NON-COMPETING CONTINUATION	$382,724
														Subtotal = $382,724

Issue Date FY: 2023 ( Subtotal = $381,754 )
2023	2023	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Vision Research	000	3	6/12/2023	NON-COMPETING CONTINUATION	$381,754
														Subtotal = $381,754

Issue Date FY: 2022 ( Subtotal = $371,242 )
2022	2022	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Vision Research	000	2	6/6/2022	NON-COMPETING CONTINUATION	$371,242
														Subtotal = $371,242

Issue Date FY: 2021 ( Subtotal = $424,751 )
2021	2021	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Vision Research	000	1	6/10/2021	NEW	$424,751
														Subtotal = $424,751

Grand Total All Awards = $1,560,465

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Mechanisms of intrinsic light responses in the ocular lens

Award Number: R01EY032752

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2021

PERIOD OF PERFORMANCE END DATE: 05/31/2025

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