The Efemp1R345W Macular Dystrophy Mutation Causes Amplified Circadian and Photophobic Responses to Light in Mice

Stewart Thompson; Frederick R Blodi; Demelza R Larson; Michael G Anderson; Steven F Stasheff

doi:10.1167/iovs.19-26881

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The Efemp1R345W Macular Dystrophy Mutation Causes Amplified Circadian and Photophobic Responses to Light in Mice

Journal article

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Peer reviewed

The Efemp1R345W Macular Dystrophy Mutation Causes Amplified Circadian and Photophobic Responses to Light in Mice

Stewart Thompson, Frederick R Blodi, Demelza R Larson, Michael G Anderson and Steven F Stasheff

Investigative ophthalmology & visual science, Vol.60(6), pp.2110-2117

05/01/2019

DOI: 10.1167/iovs.19-26881

PMCID: PMC6735810

PMID: 31095679

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Abstract

The R345W mutation in EFEMP1 causes malattia leventinese, an autosomal dominant eye disease with pathogenesis similar to an early-onset age-related macular degeneration. In mice, Efemp1R345W does not cause detectable degeneration but small subretinal deposits do accumulate. The purpose of this study was to determine whether there were abnormal responses to light at this presymptomatic stage in Efemp1R345W mice. Responses to light were assessed by visual water task, circadian phase shifting, and negative masking behavior. The mechanism of abnormal responses was investigated by anterior eye exam, electroretinogram, melanopsin cell quantification, and multielectrode recording of retinal ganglion cell activity. Visual acuity was not different in Efemp1R345W mice. However, amplitudes of circadian phase shifting (P = 0.016) and negative masking (P < 0.0001) were increased in Efemp1R345W mice. This phenotype was not explained by anterior eye defects or amplified outer retina responses. Instead, we identified increased melanopsin-generated responses to light in the ganglion cell layer of the retina (P < 0.01). Efemp1R345W increases the sensitivity to light of behavioral responses driven by detection of irradiance. An amplified response to light in melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) is consistent with this phenotype. The major concern with this effect of the malattia leventinese mutation is the potential for abnormal regulation of physiology by light to negatively affect health.

Animals

Circadian Rhythm - physiology

Disease Models, Animal

Electroretinography

Extracellular Matrix Proteins - genetics

Macular Degeneration - genetics

Macular Degeneration - physiopathology

Mice

Mice, Inbred C57BL

Mutation

Perceptual Masking - physiology

Phenotype

Photophobia - physiopathology

Retinal Ganglion Cells - physiology

Rod Opsins - physiology

Visual Acuity - physiology

Details

Title: Subtitle: The Efemp1R345W Macular Dystrophy Mutation Causes Amplified Circadian and Photophobic Responses to Light in Mice
Creators: Stewart Thompson - Institute for Vision Research, University of Iowa, Iowa City, Iowa, United States
Frederick R Blodi - Ophthalmology and Visual Sciences, University of Louisville, Louisville, Kentucky, United States
Demelza R Larson - Biology Department, College of St. Benedict & St. John's University, Collegeville, Minnesota, United States
Michael G Anderson - VA Center for Prevention and Treatment of Visual Loss, Iowa City, Iowa, United States
Steven F Stasheff - George Washington University School of Medicine and Health Sciences, Washington, DC, United States
Resource Type: Journal article
Publication Details: Investigative ophthalmology & visual science, Vol.60(6), pp.2110-2117
DOI: 10.1167/iovs.19-26881
PMID: 31095679
PMCID: PMC6735810
NLM abbreviation: Invest Ophthalmol Vis Sci
ISSN: 0146-0404
eISSN: 1552-5783
Grant note: R21 EY029609 / NEI NIH HHS I01 RX001481 / RRD VA P30 EY025580 / NEI NIH HHS
Language: English
Date published: 05/01/2019
Academic Unit: Molecular Physiology and Biophysics; Ophthalmology and Visual Sciences
Record Identifier: 9984172169302771

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