Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment worldwide. AMD development is associated with inflammation, oxidative stress, and a progressive proteostasis imbalance, in whose regulation, c-Jun N-terminal kinases (JNKs) play a crucial role. JNK inhibition is being discussed as a new way to prevent and treat AMD, but there are no data on JNK signaling in the retina and its changes with age and with AMD development. Here, for the first time, we assessed JNK-signaling activity in the retina and did not detect its age-related changes in healthy Wistar rats. By contrast, manifestation and progression of the AMD-like pathology in OXYS rats occurred simultaneously with JNK pathway activation. We also confirmed that selective JNK3 inhibitor 11H-indeno[1,2-b] quinoxalin-11-one oxime sodium salt (IQ-1S) can suppress neurodegenerative changes in the OXYS rat retina. Its effects were prevention of the destructive changes in retinal synapses and the suppression of the JNK signaling pathway activity during active progression of AMD signs in OXYS rats.

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder and the leading cause of senile dementia. The key risk factor for a more common (>95

Purpose: to assess the reaction of multipolar retinal neurons to light irradiation depending on the intensity and duration of exposure. Material and methods. Outbred sexually mature white rats (n = 50, 100 eyes) weighing 180–200 g were exposed to continuous round-the-clock light (200, 3,500 lux; 1, 2, 7, 14, 30 days). The control group consisted of 25 non-irradiated animals (50 eyes). Using semifine sections, colored with toluidine blue, we counted the number of neurons in the ganglionic layer with karyopyknosis, focal and total chromatolysis. In the optic nerve, the percentage of degeneratively altered axons and the number of nerve fibers with deformation of the myelin sheath were calculated. Ultrastructural changes in neurons were studied using a JEM-100 CX-II electron microscope. Results. In the first days of the experiment (1, 2 days), reactive and destructive changes in organelles are observed in the perikaryons of multipolar retinal neurons. The granular endoplasmic reticulum becomes fragmented, loses part of its ribosomes, and vacuoles of varied sizes are formed from its cisterns. With an increase in the duration of exposure (7–30 days), degradation processes are increasing, all the more so after high-intensity (3,500 lux) light irradiation. The photodamage causes changes in all components of the optic nerve and is characterized by a destruction of organelles, a decrease in the number of elements of the cytoskeleton in the axon, and myelin sheath splitting. Conclusion. Changes in multipolar neurons of the retina after photodamage are primarily related to the content and distribution of the chromatophilic substance and depend on the intensity and duration of illumination.

Visomitin eye drops are the first and, so far, the only drug based on SkQ1 – the mitochondria-targeted antioxidant 10-(6′-plastoquinonyl) decyltriphenylphosphonium, developed in the laboratories of Moscow State University under the leadership of Academician V. P. Skulachev. SkQ1 is considered as a potential tool to combat the aging program. We have previously shown that it is able to prevent and/or suppress development of all manifestations of accelerated senescence in OXYS rats, including retinopathy, similar to the age-related macular degeneration (AMD). Here, we assessed the effect of Visomitin instillations on progression of the AMD-like pathology and p38 MAPK and ERK1/2 activity in the OXYS rat retina (from the age of 9 to 12 months). Wistar and OXYS rats treated with placebo (composition identical to Visomitin with the exception of SkQ1) were used as controls. Ophthalmological examination showed that in the OXYS rats receiving placebo, retinopathy progressed and severity of clinical manifestations did not differ from the intact OXYS rats. Visomitin suppressed progression of the AMD-like pathology in the OXYS rats and significantly improved structural and functional parameters of the retinal pigment epithelium cells and state of microcirculation in the choroid, which, presumably, contributed to preservation of photoreceptors, associative and ganglion neurons. It was found that the activity of p38 MAPK and ERK1/2 in the retina of 12-month-old OXYS rats is higher than that of the Wistar rats of the same age, as indicated by the increased content of phosphorylated forms of p38 MAPK and ERK1/2 and their target protein tau (at position T181 and S396). Visomitin decreased phosphorylation of p38 MAPK, ERK1/2, and tau indicating suppression of activity of these MAPK signaling cascades. Thus, Visomitin eye drops are able to suppress progression of the AMD-like pathology in the OXYS rats and their effect is associated with the decrease in activity of the MAPK signaling cascades.

The morphofunctional features of the ovaries were evaluated in rats with functional ovarian cysts model treated with gonadotropin-releasing hormone antagonist. Administration of the antagonist significantly ( p =0.009) reduced the number of cysts and the growth of follicles in the ovaries. The obtained results attest to a possibility of successful treatment of functional ovarian cysts with gonadotropin-releasing hormone antagonist.

We studied the expression of insulin-like growth factor 1 (IGF-1), androgen receptor (AR) and luteinizing hormone receptor (LHR) in the ovaries under the conditions of the modeling and subsequent treatment of functional ovarian cysts with gonadotropin-releasing hormone antagonist (ant-GnRH). The intensity of IGF-1, LHR, and AR expression in the generative elements of rat ovaries changed under conditions of functional ovarian cysts simulation, as well as during treatment with ant-GnRH. In both experimental groups, the expression levels of the studied markers in preantral follicles and epithelial lining of cysts were found to be related to the number of growing follicles and cysts. A divergence of LHR and AR expression indices and a more pronounced decrease in the number of cystic cavities were observed in the group receiving ant-GnRH. These changes demonstrate a positive effect of ant-GnRH on intra-ovarian regulatory factors and a therapeutic effect in functional ovarian cysts.

Objectives. To assess the influences of prenatal alcoholization on the formation of various structural components of the brain in human embryos. Materials and methods. The study examined 26 specimens of embryonic material at 8–11 weeks of intrauterine development. Specimens were divided into four subgroups depending on developmental period (Control 1 at 8–9 weeks of development and Control 2 at 10–11 weeks of development) and maternal medical history (presence or absence of a diagnosis of “alcoholism stages I–II” in the medical history). Morphometry was run on Nissl-stained semithin sections. Diameters and areas of each individual tissue element (neuroblasts, glioblasts, vessels of the micricirculatory bed (MCB)) were determined, along with specific areas (the ratio of the total area of the structure under study to the area of the entire section); mean numbers of these structures per unit area of sections were also calculated. Morphometric analysis was run in AxioVision 4.8 (Carl Zeiss, Germany) and statistical analysis of differences between study cohorts used the Mann–Whitney test (differences taken as significant at p < 0.05). Results: As compared with the intact groups, the alcohol groups showed insufficient increases in the area of MCB vessels, combined with compensatory increases in the numbers of vessels per unit area on sections (48.5 and 83.3 μm2, respectively, p < 0.05). Comparison of glioblast sizes in the control and alcohol subgroups at different stages of development (average area 21.3 and 32.1 μm2; 12.9 and 13.3 μm2, respectively) revealed a delay in the increase in size of cellular structures in alcoholized groups at the initial stages, while comparison of data at later periods revealed no significant difference, though there was an increase in the specific number of cells in subgroup A2 (p < 0.05). Neuroblasts also showed a decrease in cell size with increasing development time in both the control and the alcohol subgroups. However, cell size in group A2 was greater than that in group C2, while the number of these cells was smaller (p < 0.05). Conclusions. Alcohol led to changes in the sizes and numbers of neuroblasts, glioblasts, and MCB vessels and, as a consequence, to disproportionality in the development of all brain tissue. Changes progressed with increasing development time.

Aim. To study the response of retinal glial cells to constant irradiation of various intensity and to develop a mathematical model allowing to evaluate the dynamics of damage to radial glial cells and predict their photodamage depending on the duration and intensity of irradiation. Materials and methods. Outbred sexually mature white rats ( n = 50) weighing 180–200 g were exposed to constant round-the-clock light (200, 3,500 lux, days 1, 2, 7, 14, 30). The control group consisted of 25 non-irradiated animals. Using semi-thin sections stained with toluidine blue, we counted the number of pycnomorphic cells in the radial glial cells. Ultrastructural changes in the glial cells were studied using the JEM-100 CX-II electron microscope. Results. The study showed that after photodamage, oligodendrocytes and astrocytes were mainly characterized by mitochondrial swelling and expansion of endoplasmic reticulum cisterns. Microglial cells at the late stage of the experiment (day 30) were localized in the inner layers of the retina; their density depended on the intensity of irradiation. The earliest (days 1, 2) changes in the radial glial cells were noted in the subretinal space and were manifested by proliferation of scleral processes and phagocytosis of dead sensorineural cell fragments. The intensification of destructive changes in the radial glial cells led to disturbances in neuron – glia interactions in the retina and a decrease in regeneration of retinal neurons (day 7–14). The developed mathematical model allowed to assess the dynamics of damage to the radial glial cells in the retina and to predict photodamage depending on the duration and intensity of irradiation. Conclusion. Glial responses in the retina after photodamage depend on the intensity and duration of light exposure. As the duration of irradiation increases, degenerative changes in glial cells intensify and are more pronounced after high (3,500 lux) irradiation intensity.

The aim. To conduct a comparative analysis of clinical and anamnestic data in women of reproductive age after ovarian cyst surgery and with occult premature ovarian insufficiency (POI) to predict a poor ovarian response to stimulation. Materials and methods. We conducted a retrospective study of medical records of women (aged 18–40 years) with infertility at the Assisted Reproductive Technology Center of Siberian State Medical University from 2017 to 2020. The main group consisted of 84 patients who underwent ovarian cyst surgery. The comparison group consisted of 33 patients with biochemical signs of POI (follicle stimulating hormone (FSH) 10–12 mMU / ml) who did not undergo ovarian cyst surgery. Anti-Mullerian hormone (AMH), FSH, estradiol, the antral follicle count (AFC), and the ovarian response to stimulation were compared. Results. A correlation was established between AFC and a poor ovarian response both in the main group ( r = –0.7; p = 0.004) and in the comparison group ( r = –0.620; p = 0.000) in women under 35 years of age. A correlation was found between the concentration of estradiol and a poor ovarian response in the comparison group in women over 35 years of age ( r = –0.707; p = 0.001). A moderate negative correlation between AMH and a poor ovarian response was revealed only in the main group of women under the age of 35 years ( r = –0.589; p = 0.021). A moderate negative correlation between AMH and a poor ovarian response was revealed in the comparison group in women under the age of 35 years ( r = –0.648; p = 0.000), a weak negative correlation was found for women at the age of 35 years ( r = –0.500; p = 0.004). In both groups, the level of FSH did not determine the ovarian response to stimulation. Conclusion. The determination of AFC and AMH is more significant in predicting a poor ovarian response in women after ovarian surgery and in women with occult signs of POI under the age of 35 years, compared with FSH. In the group of women over 35 years with occult signs of POI, the concentration of estradiol may matter in predicting a poor ovarian response, which requires further research.

Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment worldwide. The development of AMD is associated with inflammation, oxidative stress, and progressive proteostasis imbalance, in the regulation of which c-Jun N-terminal kinases (JNK) play a crucial role. JNK inhibition is discussed as an alternative way for prevention and treatment of AMD and other neurodegenerative diseases. Here we assess the retinoprotective potential of the recently synthesized JNK inhibitor 11H-indeno[1,2-b]quinoxalin-11-one oxime sodium salt (IQ-1S) using senescence-accelerated OXYS rats as a model of AMD. The treatment with IQ-1S (50 mg/kg body weight intragastric) during the period of active disease development (from 4.5 to 6 months of age) improved some (but not all) histological abnormalities associated with retinopathy. IQ-1S improved blood circulation, increased the functional activity of the retinal pigment epithelium, reduced the VEGF expression in the endothelial cells, and increased the expression of PEDF in the neuroretina. The result was a decrease in the degeneration of photoreceptors and neurons of the inner layers. IQ-1S significantly improved the retinal ultrastructure and increased the number of mitochondria, which were significantly reduced in the neuroretina of OXYS rats compared to Wistar rats. It seems probable that using IQ-1S can be a good prophylactic strategy to treat AMD.

This review deals with the current state of affairs in the diagnosis of cervical squamous intraepithelial lesions. Transformation of classifications of cervical pathologies is considered. The role of cytological (liquid-based and conventional cytology), molecular biological (Digene Hybrid Capture test), immunohistochemical (p16INK4α, Ki-67), and histologic methods in the diagnosis of cervical lesions is discussed. Particular attention is paid to the diagnosis of human papillomavirus infection. Performance indicators of screening programs based on primary determination of human papillomavirus (HPV) DNA in comparison with common cytological methods are presented. Tropism of HPV to various parts of the cervix, which predisposes to the formation of deep multifocal lesions, as well as the influence of the physical status of HPV on the treatment strategy and risks of relapse are considered.

— According to the Alzheimer’s Disease International (ADI) international organization about 50 million people in the world suffer from Alzheimer’s disease (AD). However, there are no effective methods for preventing or slowing the progression of AD. Inhibition of the c-Jun N-terminal kinase (JNK) signaling pathway is discussed below as an alternative way to prevent the development of AD and other neurodegenerative diseases. In the present study, we evaluated the ability of a recently synthesized selective JNK3 inhibitor, 11 H -indeno[1,2- b ]quinoxalin-11-one oxime sodium salt (IQ-1S), to suppress neurodegenerative processes in OXYS rats at an early stage of development of AD at the ages of 4.5 to 6 months. Treatment with IQ-1S (50 mg/kg intragastrically) led to the suppression of the development of neurodegenerative processes in the cerebral cortex of OXYS rats: an increase in the proportion of unchanged neurons, a decrease in the proportion of neurons with signs of destruction and irreversible damage, and a normalization of the glioneuronal index, which was facilitated by a decrease in the severity of hyperviscosity syndrome blood in OXYS rats. The use of the IQ-1S JNK3 inhibitor may be a promising strategy for the prevention of early neurodegenerative disorders and, possibly, the treatment of AD.

Background. There are different opinions about the effect of functional ovarian cysts on the duration of controlled ovarian hyperstimulation, the dose of gonadotropins, the number and quality of collected oocytes and produced embryos, and the frequency of pregnancy. Aim. To analyze in vitro fertilization (IVF) programs in women with anovulatory infertility and ovarian retention. Materials and methods. A prospective study included 71 women aged 18–44 years. The main group (I) included patients ( n = 38) with anovulatory infertility and functional ovarian cysts (FOC) diagnosed by ultrasound before enrollment in the IFV program. Patients of this group underwent ultrasound-guided transvaginal puncture of ovarian cyst followed by cytology. The comparison group (II) ( n = 33) encompassed patients with anovulatory infertility without FOC, who went through the IVF program. The control group (III) included apparently healthy individuals ( n = 15). The study algorithm included collection of clinical and anamnestic data of the patients, data of laboratory and instrumental studies, parameters of a stimulated IVF cycle, characteristics of oogenesis and early embryogenesis, and assessment of IVF program effectiveness. Conclusion. It was established that in FOC and anovulatory infertility, the number of collected oocytes was smaller; however, the number of the best quality embryos and the frequency of pregnancy did not differ.

Morphofunctional changes in microvasculature play an important role in the nerve cell plasticity, the ability to change their functional state under the influence of various factors. The aim of the research was to study the morphology of the microvasculature vessels, surrounding neurons and glia cells in the primary visual cortex of 3- and 18-month-old rats in norm and under stress caused by high-intensity twenty-four-hour light exposure, as well as under correction. Materials and Methods. The experiments were carried out on 60 Wistar male rats, aged 3- and 18-months. The authors used light and electron microscopy, and morphometry to evaluate: capillary surface area and density, surface area of altered vessels (due to stasis, sludge of formed elements and thrombosis) and unchanged ones, as well as the morphology of the surrounding cells. The Kruskal-Wallis test was used for multiple comparisons within age groups, while Mann-Whitney test was used for pair comparison. Results. The authors observed different capillary reactions to light exposure in 3- and 18-month-old rats. It resulted in an increase of capillary density in 3-month-old rats and in a decrease of capillary density in 18-month-old rats (p≤0.05). Destructive changes in neurons and glia cells were more evident in 18-month-old rats. P-tyrosol administration in 3- and 18-month-old rats with light exposure led to an increase in capillary density (p≤0.05). Under correction, young rats also demonstrated an increase in the capillary surface area, and the number of glia cells and capillaries by 1 neuron (p≤0.05). Conclusion Thus, p-tyrosol improved microvascularization in the primary visual cortex under high-intensity long-term light exposure. Keywords: microcirculation, p-tyrosol, stress, primary visual cortex. Морфофункциональные изменения микроциркуляторного русла играют важную роль в пластичности нервных клеток, их способности менять свое функциональное состояние при воздействии различных факторов. Целью исследования являлось изучение морфологии сосудов микроциркуляторного русла и окружающих их нейронов и глиоцитов в первичной зрительной коре 3- и 18-месячных крыс в норме и при стрессе, вызванном высокоинтенсивным круглосуточным световым воздействием, а также в условиях коррекции. Материалы и методы. Эксперименты выполнены на 60 крысах-самцах линии «Вистар». Возраст – 3 и 18 мес. Методами световой и электронной микроскопии, морфометрии оценивали удельную площадь и численную плотность капилляров, удельную площадь измененных (со стазом, сладжем форменных элементов и тромбозом) и неизмененных сосудов, а также морфологию клеток, их окружающих. Для множественных сравнений внутри возрастных групп использовали критерий Крускала–Уоллиса, для парных – Манна–Уитни. Результаты. У 3- и 18-месячных крыс обнаружена различная реакция капилляров на световое воздействие, что выражалось в увеличении численной плотности капилляров у 3-месячных крыс и снижении – у 18-месячных (р≤0,05). Деструктивные изменения нейронов и глиоцитов более выражены у 18-месячных крыс. Коррекция п-тирозолом у 3- и 18-месячных крыс со световым воздействием приводила к увеличению численной плотности капилляров (р≤0,05). У молодых крыс при коррекции также отмечалось увеличение удельной площади капилляров, количества глиоцитов и капилляров на 1 нейрон (р≤0,05). Заключение. Применение п-тирозола улучшало состояние микроваскуляризации в первичной зрительной коре в условиях высокоинтенсивного длительного светового воздействия. Ключевые слова: микроциркуляция, п-тирозол, стресс, первичная зрительная кора.

An experiment using 20 white male Wistar rats has shown that exposure to 3500 lux of light for 7 days causes morphological changes in the II, IV, and V layers of the primary visual cortex. This was seen in an increased percentage of reversibly and irreversibly altered neurons, mainly in the fourth layer of 18-month-old rats (p ≤ 0.05). In response to light exposure, the percentage of hyperchromic wrinkled neurons in 18‑month-old rats rises to 6% (5; 8.5), the percentage of neurons with total chromatolysis rises to 10% (8.5; 14) compared to a 1% (0.5; 14) and 6% (5; 8) rise in 3-month-old rats respectively (p ≤ 0.05). The neural damage leads to a glial reaction reflected in an increased percentage of glia with signs of edema and swelling, hyperchromia without the nucleus and cytoplasm shrinkage (p ≤ 0.05), neuronophagia, and also the intrusion of the glia cells into the neuron cytoplasm for the initiation of intracellular reparation. The destructive changes are characterized by the gliacyte hyperchromia with the shrinkage of the nucleus and cytoplasm. The percentage of these gliacytes increases significantly in 18-month-old rats under the light exposure compared to the indices in young animals (p ≤ 0.05).

We developed an improved three-vessel occlusion model of global cerebral ischemia in rats. This method consists in cessation of cerebral blood flow by accessing a. carotis communis sinistra through the ventral surface of the neck as well as tr. brachiocephalicus and a. subclavia sinistra through the first intercostal space, bypassing the pleural cavity and excluding pneumothorax. After the occlusion of the vessels that resulted in interruption of their blood flow, according to laser-Doppler flowmetry, there was a sharp decline in local cerebral blood flow in the visual cortex to 4±1% of the initial level. After restoring the level of local cerebral blood flow at the 5th minute, 10th minute, 20th minute and 24th hour of reperfusion, the levels of local cerebral blood flow were 51±7%, 41±5%, 35±8% and 54±9% of the initial level, respectively. Histo-quantitative analysis of changes in neurons of the hippocampus of rats showed that after ischemic injury, the numerical density of neurons in hippocampal zone CA1 in the observed 1mm2 region decreased by 29%, 22%, and 35%, respectively, compared to sham-operated animals (p<0.05). By the first day after global cerebral ischemia, the experimental group had shown a mean neurological deficit score equal to 7.5±1.0 and 7.9±0.7 points, followed by a decrease up to score 6.5±1.1 and 5.9±0.7 on the third day, 4.6±0.8 and 4.7±0.5 on the fifth day (on chloral hydrate and propofol anesthesia correspondently).

BACKGROUND:Salidroside is a biologically active compound derived from Rhodiola rosea L. Studies showed that salidroside after i.v. injection is extensively metabolized to p-tyrosol and only trace amounts of salidroside are found in the brain tissue. OBJECTIVE:The aim of the study was to investigate the neuroprotective effects of p-tyrosol in the global cerebral ischemia-reperfusion (GCI) model. STUDY DESIGN:A total of 103 Wistar rats were assigned to groups of sham-operated (n=10), control (n=42), p-tyrosol-treated (n=36), and pentoxifylline-treated (n=15) animals. The rats of control, p-tyrosol-treated, and pentoxifylline-treated groups received intravenously 0.9% NaCl solution, 2% solution of p-tyrosol in doses of 5mg/kg, 10mg/kg, and 20mg/kg, and pentoxifylline in a dose of 100mg/kg, respectively, daily for 5 days. Rats were examined at days 1, 3, and 5 after GCI. After evaluation of neurological deficit, animals were euthanized for morphological and biochemical characterization. METHODS:Rats of control, p-tyrosol-treated, and pentoxifylline-treated groups were exposed to three-vessel model of GCI. Neurological deficit, numeric density of neurons in hippocampal CA1 region, and percentage of neurons with focal and total chromatolysis were studied. Biochemical study assessed contents of conjugated dienes and fluorescent products in brain homogenate. RESULTS:In control group, only 50.0% of rats survived by day 5 after the GCI; 38.1% of survived animals had severe neurologic deficit. In brain tissue of PTX-treated rats, the levels of diene conjugates and fluorescent products were 79% and 73%, respectivley, at day 5 compared with control. Differences in diene conjugates were statistically significant compared with control. The survival rate of animals treated with 20mg/kg p-tyrosol was 82.3% at day 5 after GCI. In p-tyrosol-treated GCI rats, the numeric density of neurons in the hippocampal CA1 region was higher by 31% compared with control. The percentage of neurons with focal and total chromatolysis decreased by 27% and 43%, respectively. At day 5 after GCI, the levels of conjugated dienes and fluorescent products were significantly lower (by 37% and 45%, respectively) in group of animals treated with 20mg/kg p-tyrosol compared with control. Moderate neuroprotective effects of 5mg/kg p-tyrosol administration were documented only at day 5 after GCI. In case of 10mg/kg p-tyrosol administration, neuroprotection was documented sooner: at day 1 or 3 after GCI. However, administration of 5 and 10mg/kg p-tyrosol did not affect animal survival. CONCLUSION:Course administration of intravenous p-tyrosol in a dose of 20mg/kg increased survival, reduced neurological deficit after GCI, attenuated neuronal damage in the hippocampus, and attenuated lipid peroxidation in brain tissue in animals subject to GCI with reperfusion.

BACKGROUND:There has been considerable interest in discovery of the genetic architecture of complex traits, particularly age-related neurodegenerative disorders. To predict disease risk and to understand its genetic basis in humans, it is necessary to study animal models. Our previous research on the accelerated-senescence OXYS strain has revealed two quantitative trait loci (QTLs) on rat chromosome 1 that are associated with early cataract and/or retinopathy as well as with behavioral abnormalities. Each locus was partially mapped within the introgressed segments in a certain congenic strain: WAG/OXYS-1.1 or WAG/OXYS-1.2. Retinal transcriptome profiling of 20-day-old congenic and OXYS rats by high-throughput RNA sequencing uncovered relevant candidate genes and pathways. Nonetheless, the question remained open whether the same genetic components simultaneously have effects on various manifestations of the accelerated-senescence phenotype in OXYS rats. The present study was designed to analyze the genes of susceptibility to early neurodegenerative processes taking place in the OXYS rat retina and brain and to assess their potential functional clustering. The study was based on the findings from recent publications (including mapping of quantitative trait loci) and on comparative phenotyping of congenic rat strains.RESULTS:The backcrossing of Wistar Albino Glaxo (WAG) and OXYS strains to generate the congenics resulted in two congenic strains with high susceptibility to cataract and retinopathy but with no obvious signs of Alzheimer's disease-like brain pathology that are specific for OXYS rats. Thus, the genes of susceptibility to brain neurodegeneration were not introgressed into the congenic strains or there is a strong effect of the genetic background on the disease phenotype. Moreover, the progression of retinopathy with age was relatively less severe in the WAG background compared to the OXYS background. A comparative analysis of previously defined QTLs and congenic segments led to identification of candidate genes with a suspected effect on brain neurodegeneration including the genes showing differential expression in the congenic strains.CONCLUSION:Overall, our findings suggest that the cause of the cataract and the cause of retinopathy phenotypes in OXYS rats may be genetically linked to each other within the introgressed segments in the WAG/OXYS-1.1 and/or WAG/OXYS-1.2 congenic strains.

Age-related macular degeneration (AMD), a neurodegenerative and vascular retinal disease, is the leading cause of blindness in the developed world. Accumulating evidence suggests that alterations in the expression of a small heat shock protein (αB-crystallin) are involved in the pathogeneses of AMD. Here we demonstrate that senescence-accelerated OXYS rats-an animal model of the dry form of AMD-develop spontaneous retinopathy against the background of reduced expression of αB-crystallin in the retina at the early preclinical stages of retinopathy (age 20 days) as well as at 4 and 24 months of age, during the progressive stage of the disease. The level of αA-crystallin expression in the retina of OXYS rats at all the ages examined was no different from that in disease-free Wistar rats. Treatment with the mitochondria-targeted antioxidant SkQ1 (plastoquinonyl-decyltriphenylphosphonium) from 1.5 to 4 months of age, 250 nmol/kg, increased the level of αB-crystallin expression in the retina of OXYS rats. SkQ1 slowed the development of retinopathy and reduced histological aberrations in retinal pigment epithelium cells. SkQ1 also attenuated neurodegenerative changes in the photoreceptors and facilitated circulation in choroid blood vessels in the retina of OXYS rats; this improvement was probably linked with the restoration of αB-crystallin expression.