RESUMO
PURPOSE: To determine whether participants with normal visual acuity, no ophthalmoscopically signs of age-related maculopathy (ARM) in both eyes, and who are carriers of the CFH, LOC387715, and HRTA1 high-risk genotypes (gene-positive) have impaired rod- and cone-mediated mesopic visual function compared with persons who do not carry the risk genotypes (gene-negative). METHODS: Fifty-three Caucasian study participants (mean 55.8 ± 6.1) were genotyped for CFH, LOC387715/ARMS2, and HRTA1 polymorphisms. Single-nucleotide polymorphisms were genotyped in the CFH (rs380390), LOC387715/ARMS2 (rs10490924), and HTRA1 (rs11200638) genes using optimized gene-expression assays. The critical fusion frequency (CFF) mediated by cones alone (long-, middle-, and short-wavelength sensitive cones, LMS) and by the combined activities of cones and rods (LMSR) were determined. The stimuli were generated using a four-primary photostimulator that provides independent control of the photoreceptor excitation under mesopic light levels. Visual function was further assessed using standard clinical tests, flicker perimetry, and microperimetry. RESULTS: The mesopic CFF mediated by rods and cones (LMSR) was significantly reduced in gene-positive compared to gene-negative participants after correction for age (P = 0.03). Cone-mediated CFF (LMS) was not significantly different between gene-positive and -negative participants. There were no significant associations between flicker perimetry and microperimetry and genotype. CONCLUSIONS: This is the first study to relate ARM risk genotypes with mesopic visual function in clinically normal persons. These preliminary results could become of clinical importance because mesopic vision may be used as a biomarker to document subclinical retinal changes in persons with risk genotypes and to determine whether those persons progress into manifest disease.
Assuntos
Degeneração Macular/genética , Visão Mesópica/genética , Polimorfismo de Nucleotídeo Único , Proteínas/genética , Serina Endopeptidases/genética , Transtornos da Visão/genética , Idoso , Fator H do Complemento/genética , Feminino , Perfilação da Expressão Gênica , Genótipo , Heterozigoto , Serina Peptidase 1 de Requerimento de Alta Temperatura A , Humanos , Degeneração Macular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Células Fotorreceptoras de Vertebrados/fisiologia , Fatores de Risco , Tomografia de Coerência Óptica , Transtornos da Visão/diagnóstico , Acuidade Visual/fisiologia , Testes de Campo VisualRESUMO
Attempts to understand circadian organization in the mammalian retina have concentrated increasingly on the mouse. However, rather little is known regarding circadian control of retinal light responses in this species. Here, the authors address this deficit using electroretinogram (ERG) recordings in C57BL/6 mice to evaluate rhythmicity in the wild-type retina and to identify the consequences of circadian clock loss in Cry1(- /-)Cry2(-/-) mice. They observe a circadian rhythm in the ERG waveform under light-adapted, cone-isolating conditions in wild-type mice, with b-wave speed and amplitude and the total power of oscillatory potentials all enhanced during the day. Wild types also exhibited a circadian dependence to ERG amplitude under dark-adapted conditions, but only when the flash stimulus was sufficiently bright to lie within the response range of cones. Cry1(-/ -)Cry2(-/-) mice lacked rhythmicity but retained superficially normal ERGs under all conditions suggesting that circadian clocks are dispensable for general retinal function. However, clock loss was associated with subtle abnormalities in retinal responses, with the amplitude of cone and mixed rod + cone ERGs constitutively enhanced. These data suggest that circadian clocks drive a fundamental fine-tuning of retinal pathways that is particularly apparent under conditions in which vision relies upon either cones alone or mixed rod + cone photoreception.
