Myopia-26, the female-limited form of early-onset high myopia, occurring in a European family

Background Female-limited early-onset high myopia, also called Myopia-26 is a rare monogenic disorder characterized by severe short sightedness starting in early childhood and progressing to blindness potentially by the middle ages. Despite the X-linked locus of the mutated ARR3 gene, the disease paradoxically affects females only, with males being asymptomatic carriers. Previously, this disease has only been observed in Asian families and has not gone through detailed investigation concerning collateral symptoms or pathogenesis. Results We found a large Hungarian family displaying female-limited early-onset high myopia. Whole exome sequencing of two individuals identified a novel nonsense mutation (c.214C>T, p.Arg72*) in the ARR3 gene. We carried out basic ophthalmological testing for 18 family members, as well as detailed ophthalmological examination (intraocular pressure, axial length, fundus appearance, optical coherence tomography, visual field- testing) as well as colour vision- and electrophysiology tests (standard and multifocal electroretinography, pattern electroretinography and visual evoked potentials) for eight individuals. Ophthalmological examinations did not reveal any signs of cone dystrophy as opposed to animal models. Electrophysiology and colour vision tests similarly did not evidence a general cone system alteration, rather a central macular dysfunction affecting both the inner and outer (postreceptoral and receptoral) retinal structures in all patients with ARR3 mutation. Conclusions This is the first description of a Caucasian family displaying Myopia-26. We present two hypotheses that could potentially explain the pathomechanism of this disease.

Myopia-26, the female-limited form of early-onset high myopia, occurring in a European family

Background: Female-limited early-onset high myopia, also called Myopia-26 is a rare monogenic disorder characterized by severe short sightedness starting in early childhood and progressing to blindness potentially by the middle ages. Despite the X-linked locus of the mutated ARR3 gene, the disease paradoxically affects females only, with males being asymptomatic carriers. Previously, this disease has only been observed in Asian families and has not gone through detailed investigation concerning collateral symptoms or pathogenesis Results: We found a large Hungarian family displaying female-limited early-onset high myopia. Whole exome sequencing of two individuals identified a novel nonsense mutation (c.214C>T, p.Arg72*) in the ARR3 gene. We carried out basic ophthalmological testing for 18 family members, as well as detailed ophthalmological examination (intraocular pressure, axial length, fundus appearance, optical coherence tomography, visual field- testing) as well as colour vision- and electrophysiology tests (standard and multifocal electroretinography, pattern electroretinography and visual evoked potentials) for eight individuals. Ophthalmological examinations did not reveal any signs of cone dystrophy as opposed to animal models. Electrophysiology and colour vision tests similarly did not evidence a general cone system alteration, rather a central macular dysfunction affecting both the inner and outer (postreceptoral and receptoral) retinal structures in all patients with ARR3 mutation. Conclusions: This is the first description of a Caucasian family displaying Myopia-26. We present two hypotheses that could potentially explain the pathomechanism of this disease.

Myopia-26, the female-limited form of early-onset high myopia, occurring in a European family

Background: Female-limited early-onset high myopia, also called Myopia-26 is a rare monogenic disorder characterized by severe short sightedness starting in early childhood and progressing to blindness potentially by the middle ages. Despite the X-linked locus of the mutated ARR3 gene, the disease paradoxically affects females only, with males being asymptomatic carriers. Previously, this disease has only been observed in Asian families and has not gone through detailed investigation concerning collateral symptoms or pathogenesisResults: We found a large Hungarian family displaying female-limited early-onset high myopia. Whole exome sequencing of two individuals identified a novel nonsense mutation (c.214C>T, p.Arg72*) in the ARR3 gene. We carried out basic ophthalmological testing for 18 family members, as well as detailed ophthalmological examination (intraocular pressure, axial length, fundus appearance, optical coherence tomography, visual field- testing) as well as colour vision- and electrophysiology tests (standard and multifocal electroretinography, pattern electroretinography and visual evoked potentials) for eight individuals. Ophthalmological examinations did not reveal any signs of cone dystrophy as opposed to animal models. Electrophysiology and colour vision tests similarly did not evidence a general cone system alteration, rather a central macular dysfunction affecting both the inner and outer (postreceptoral and receptoral) retinal structures in all patients with ARR3 mutation. Conclusions: This is the first description of a Caucasian family displaying Myopia-26. We present two hypotheses that could potentially explain the pathomechanism of this disease.

Clinical polymorphism and genetic heterogeneity of inherited retinal diseases

Наследственные заболевания сетчатки (НЗС) представляют собой класс офтальмологических болезней, в котором выделяют заболевания с преимущественным поражением палочковой системы и заболевания с преимущественным поражением колбочковой системы, включающие макулярные дистрофии. В представленном сообщении описана структура спектра НЗС в клинически полиморфной выборке на основании данных клинических, инструментальных (оптической когерентной томографии, аутофлюоресценции, электроретинографии) и молекулярно-генетических методов диагностики (NGS, секвенирование по Сэнгеру). Inherited retinal disease (IRD) is a class of ophthalmic disorders in which can be classified into diseases of primarily of rod system and with primarily of cone system, which include macular dystrophies. In the presented report the structure of spectrum of IRD in clinically polymorphic is presented on the base of clinical, molecular-genetics and instrumental (OCТ, autofluorescencе, eletroretinography).

Rest-activity cycles and melatonin phase angle of circadian entrainment in people without cone-mediated vision

Light is strong zeitgeber to the human circadian system, entraining internal rhythms in physiology and behaviour to the external world. This is mediated by the melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs), which sense light in addition to the classical photoreceptors, the cones and rods. Circadian responses depend on light intensity, with exposure to brighter light leading to bigger circadian phase shifts and melatonin suppression. In congenital achromatopsia (prevalence 1 in 30,000 to 50,000 people), the cone system is non-functional, resulting in light avoidance and photophobia at light levels which are tolerable and habitual to individuals with a normal, trichromatic retina. Here, we examined chronotype and self-reported sleep, actigraphy-derived rest-activity cycles and increases melatonin in the evening in a group of genetically confirmed congenital achromats. We found normal rest-activity patterns in all participants, and normal melatonin phase angles of entrainment in 2/3 of our participants. Our results suggest that a functional cone system and exposure to daytime light intensities are not necessary for regular behavioural and hormonal entrainment. This may point to a compensation mechanism in circadian photoreception, which in conjunction with non-photic zeitgebers, ensures synchronisation of activity to the external world.Significance statementRhythms in physiology and behaviour are synchronised to the external cycle of light exposure. This is mediated by the retinohypothalamic tract, which connects the photoreceptors in the eye with the “circadian pacemaker” in our brain, the suprachiasmatic nucleus. What happens to our circadian rhythm when we lack the cone photoreceptors in the eye that enable us to see in daylight? We examined this question in a group of rare congenital achromats. Our work reveals that normal rhythms in rest and activity, and production of hormones, does not require a functional cone system.

Electrogenesis of Retina and Optic Nerve after Vitrectomy for the Primary Full-Thickness Macular Hole

Purpose. To study the dynamics of electrophysiological parameters of the retina and optic nerve after vitrectomy for a primary fullthickness macular hole.Patients and Methods. Electrophysiological examination was performed in 40 patients (40 eyes) before vitrectomy, on the 1st, 3rd, 7th, 14th, 30th, 60th, 180th day after the operation. Three groups of patients were formed depending on the intraocular tamponade: the first group — air tamponade, the second group — gas (C3F8) tamponade, the third group — silicone oil tamponade.Results. In the first, second and third groups significant decrease in the retinal and optic nerve electrogenesis was revealed on the 1st day (p < 0.001) after vitrectomy. By the end of observation period all electrophysiological indices in the first, second and third groups recover to normal levels, excluding the retinal cone system and optic nerve parameters in the third group. Electrophysiological indices recovered twice as slow in the second group, compared to the first group, due to C3F8 gas tamponade inhibitory effect. In the first and second groups the photoreceptors recovered twice as fast as bipolar cells.Conclusions. Vitrectomy causes significant inhibition of photoreceptors, bipolar and ganglion cells electrogenesis. The duration of vitrectomy is a significant negative factor determining retinal and optic nerve electrogenesis inhibition in the postop. Intraocular C3F8 gas, silicon oil tamponade (compared to air tamponade) is a significant adverse factor affecting retinal and optic nerve electrogenesis inhibition in the postop. The primary full-thickness macular hole diameter is a significant factor in inhibiting electrogenesis of the retinal cone system. Photoreceptors have a greater rehabilitation ability than bipolar cells.

Complexes of clay minerals of quaternary sediments in canyon-cone system of the river Shahe (Black Sea)

A distribution of clay minerals in Quaternary sediments are revealed in the sedimentary system canyon — deep-water cone of the Shahe river in the Black sea. It is established that the ratio of illite, chlorite, smectite and kaolinite sustained by area and section is determined by the transfer of sedimentary material by turbidity flows through the canyon with the formation of a unified mineralogical province.

Electrophysiological findings show generalised post-photoreceptoral deficiency in macular telangiectasia type 2

BackgroundPhotoreceptor damage, reported in single observations, has been suggested to contribute to the disease pathogenesis in macular telangiectasia type 2 (MacTel2). The purpose of this study was to ascertain whether the photoreceptor or post-photoreceptoral function is affected in MacTel2 and could be detected using electrophysiological examination.MethodsThirty-five eyes from 18 patients (15 men, aged 60.1±9.6 years, range 38–77 years) with MacTel2 were included in the study. All patients underwent standard ophthalmic examination followed by pattern electroretinography (PERG) and full-field ERG. The data were compared against 22 normal control subjects (10 men, age 59.83±6.28 years, range 48–76).ResultsMean PERG P50 amplitude and peak time in patients with MacTel2 did not differ significantly from control values (p>0.2) but P50 amplitude was subnormal in three patients. The mean scotopic rod b-wave amplitude was significantly lower in patients than in healthy controls (p=0.027). A lower dark-adapted 10.0 b-wave (p=0.06) but not a-wave amplitude (p=0.58) was present in patients with MacTel2. Photopic single-flash a-wave and b-wave amplitudes did not differ between patient and control groups (p=0.2 and 0.3), but 30 Hz flicker peak time was significantly later in patients with MacTel2 with no effect on amplitude (p=0.04 and 0.7).ConclusionBoth scotopic (rod system dominated) and photopic ERGs (cone system) are consistent with post-photoreceptoral dysfunction. There was no electrophysiological evidence of dysfunction at the level of the photoreceptor.