The Efemp1R345W Macular Dystrophy Mutation Causes Amplified Circadian and Photophobic Responses to Light in Mice.
Invest Ophthalmol Vis Sci
; 60(6): 2110-2117, 2019 05 01.
Article
em En
| MEDLINE
| ID: mdl-31095679
ABSTRACT
Purpose:
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.Methods:
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.Results:
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).Conclusions:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas da Matriz Extracelular
/
Ritmo Circadiano
/
Fotofobia
/
Degeneração Macular
/
Mutação
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Invest Ophthalmol Vis Sci
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos