scholarly journals Retinal morphological and functional changes in an animal model of retinitis pigmentosa

2013 ◽  
Vol 30 (3) ◽  
pp. 77-89 ◽  
Author(s):  
BIN LU ◽  
CATHERINE W. MORGANS ◽  
SERGEY GIRMAN ◽  
RAYMOND LUND ◽  
SHAOMEI WANG
Keyword(s):  
Retinitis Pigmentosa ◽  
Retinal Degeneration ◽  
Light Adaptation ◽  
Morphological Changes ◽  
Horizontal Cell ◽  
Opsin Gene ◽  
Transgenic Rat ◽  
Functional Changes ◽  
Cone Function ◽  
Rod Function

AbstractThe P23H-1 transgenic rat carries a mutated mouse opsin gene, in addition to endogenous opsin genes, and undergoes progressive photoreceptor loss that is generally characteristic of human autosomal dominant retinitis pigmentosa (RP). Here, we examined morphological changes correlated with visual function that is comparable to clinical application in the pigmented P23H-1 rat retina as photoreceptor degeneration progressed. We found that rod function was compromised as early as postnatal day 28 and was a good indicator for tracking retinal degeneration. Cone function was normal and did not change until the thickness of the photoreceptor layer was reduced by 75%. Similar to the threshold versus intensity curves used to evaluate vision of RP patients, light-adaptation curves showed that cone thresholds depended on the number of remaining functioning cones, but not on its length of outer segments (OS). By 1 year of age, both rod and cone functions were significantly compromised. Correlating with early abnormal rod function, rods and related secondary neurons also underwent progressive degeneration, including shortening of inner and OS of photoreceptors, loss of rod bipolar and horizontal cell dendrites, thickening of the outer Müller cell processes, and reduced density of pre- and postsynaptic markers. Similar early morphological modifications were also observed in cones and their related secondary neurons. However, cone function was maintained at nearly normal level for a long period. The dramatic loss of rods at late stage of degeneration may contribute to the dysfunction of cones. Attention has to be focused on preserving cone function and identifying factors that damage cones when therapeutic regimes are applied to treat retinal degeneration. As such, these findings provide a foundation for future studies involving treatments to counter photoreceptor loss.

scholarly journals Spatial and temporal resolution of the photoreceptors rescue dynamics after treatment with voretigene neparvovec

2021 ◽  
pp. bjophthalmol-2020-318286
Author(s):  
Krunoslav Stingl ◽  
Melanie Kempf ◽  
Karl U Bartz-Schmidt ◽  
Spyridon Dimopoulos ◽  
Felix Reichel ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Objective Evaluation ◽  
Full Field ◽  
Functional Changes ◽  
Retinal Dystrophies ◽  
Retinotopic Maps ◽  
Cone Function ◽  
Visual Acuity Testing ◽  
Rod Function ◽  
The Individual

BackgroundVoretigene neparvovec is a gene therapeutic agent for treatment of retinal dystrophies caused by bi-allelic RPE65 mutations. In this study, we report on a novel and objective evaluation of a retinotopic photoreceptor rescue.MethodsSeven eyes of five patients (14, 21, 23, 24, 36 years, 1 male, 4 females) with bi-allelic RPE65 mutations have been treated with voretigene neparvovec. The clinical examinations included visual acuity testing, dark-adapted full-field stimulus threshold (FST), dark-adapted chromatic perimeter (DAC) with a 30-degree grid, and a 30 degrees grid scotopic and photopic chromatic pupil campimetry (CPC). All evaluations and spectral domain optical coherence tomography were performed at baseline, 1 month and 3 months.ResultsAll except the oldest patient had a measurable improvement of the rod function assessed via FST, DAC or scotopic CPC at 1 month. The visual acuity improved slightly or remained stable in all eyes. A cone function improvement as measured by photopic CPC was observed in three eyes. The gain of the dark-adapted threshold with blue FST and the DAC stimuli (cyan) average correlated strongly with age (R2>0.7). The pupil response improvement in the scotopic CPC correlated with the baseline local retinal volume (R2=0.5).ConclusionsThe presented protocols allow evaluating the individual spatial and temporal effects of gene therapy effects. Additionally, we explored parameters that correlated with the success of the therapy. CPC and DAC present new and fast ways to assess functional changes in retinotopic maps of rod and cone function, measuring complementary aspects of retinal function.

scholarly journals A rat model for retinitis pigmentosa with rapid retinal degeneration enables drug evaluation in vivo

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Chisato Inoue ◽  
Tamaki Takeuchi ◽  
Akira Shiota ◽  
Mineo Kondo ◽  
Yuji Nshizawa
Keyword(s):  
Retinitis Pigmentosa ◽  
Retinal Degeneration ◽  
Rat Model ◽  
Photoreceptor Cell ◽  
Photoreceptor Cells ◽  
Therapeutic Agents ◽  
Transgenic Rat ◽  
Cell Degeneration ◽  
Rat Strain

Abstract Background Although retinitis pigmentosa (RP) is most frequently studied in mouse models, rats, rabbits, and pigs are also used as animal models of RP. However, no studies have reported postnatal photoreceptor cell loss before complete development in these models. Here, we generated a transgenic rat strain, named the P347L rat, in which proline at position 347 in the rhodopsin protein was replaced with leucine. Results A pathological analysis of photoreceptor cells in the P347L rat model was performed, and drugs with potential use as therapeutic agents against RP were investigated. The data clearly showed rapid degeneration and elimination of the outer nuclear layer even before the photoreceptor cells were fully established in P347L rats. To test the usefulness of the P347L rat in the search for new therapeutic agents against RP, the effects of rapamycin on RP were investigated in this rat strain. The findings suggest that rapamycin promotes autophagy and autophagosomal uptake of the rhodopsin that has accumulated abnormally in the cytoplasm, thereby alleviating stress and delaying photoreceptor cell death. Conclusions In this RP model, the time to onset of retinal degeneration was less than that of previously reported RP models with other rhodopsin mutations, enabling quicker in vivo evaluation of drug efficacy. Administration of rapamycin delayed the photoreceptor cell degeneration by approximately 1 day.

Morphological Changes in the Rat Granulosa Cell Surface During Differentiation Induced by Estradiol and Gonadotropins

1977 ◽  
Vol 35 ◽  
pp. 484-485
Author(s):  
P. Bagavandoss ◽  
JoAnne S. Richards ◽  
A. Rees Midgley
Keyword(s):  
Cell Surface ◽  
Granulosa Cell ◽  
Morphological Changes ◽  
Follicular Development ◽  
Female Rats ◽  
Functional Changes ◽  
Group 4 ◽  
Group 3 ◽  
Group 5 ◽  
Group 2

During follicular development in the mammalian ovary, several functional changes occur in the granulosa cells in response to steroid hormones and gonadotropins (1,2). In particular, marked changes in the content of membrane-associated receptors for the gonadotropins have been observed (1).We report here scanning electron microscope observations of morphological changes that occur on the granulosa cell surface in response to the administration of estradiol, human follicle stimulating hormone (hFSH), and human chorionic gonadotropin (hCG).Immature female rats that were hypophysectcmized on day 24 of age were treated in the following manner. Group 1: control groups were injected once a day with 0.1 ml phosphate buffered saline (PBS) for 3 days; group 2: estradiol (1.5 mg/0.2 ml propylene glycol) once a day for 3 days; group 3: estradiol for 3 days followed by 2 days of hFSH (1 μg/0.1 ml) twice daily, group 4: same as in group 3; group 5: same as in group 3 with a final injection of hCG (5 IU/0.1 ml) on the fifth day.

scholarly journals Detailed Morphological Changes of Foveoschisis in Patient with X-Linked Retinoschisis Detected by SD-OCT and Adaptive Optics Fundus Camera

2015 ◽  
Vol 2015 ◽  
pp. 1-8
Author(s):  
Keiichiro Akeo ◽  
Shuhei Kameya ◽  
Kiyoko Gocho ◽  
Daiki Kubota ◽  
Kunihiko Yamaki ◽  
...  
Keyword(s):  
Adaptive Optics ◽  
Morphological Changes ◽  
Fundus Photography ◽  
Foveal Thickness ◽  
Functional Changes ◽  
Fundus Camera ◽  
Fundus Photographs ◽  
Topical Dorzolamide ◽  
Retinal Folds ◽  
Sd Oct

Purpose. To report the morphological and functional changes associated with a regression of foveoschisis in a patient with X-linked retinoschisis (XLRS).Methods. A 42-year-old man with XLRS underwent genetic analysis and detailed ophthalmic examinations. Functional assessments included best-corrected visual acuity (BCVA), full-field electroretinograms (ERGs), and multifocal ERGs (mfERGs). Morphological assessments included fundus photography, spectral-domain optical coherence tomography (SD-OCT), and adaptive optics (AO) fundus imaging. After the baseline clinical data were obtained, topical dorzolamide was applied to the patient. The patient was followed for 24 months.Results. A reportedRS1gene mutation was found (P203L) in the patient. At the baseline, his decimal BCVA was 0.15 in the right and 0.3 in the left eye. Fundus photographs showed bilateral spoke wheel-appearing maculopathy. SD-OCT confirmed the foveoschisis in the left eye. The AO images of the left eye showed spoke wheel retinal folds, and the folds were thinner than those in fundus photographs. During the follow-up period, the foveal thickness in the SD-OCT images and the number of retinal folds in the AO images were reduced.Conclusions. We have presented the detailed morphological changes of foveoschisis in a patient with XLRS detected by SD-OCT and AO fundus camera. However, the findings do not indicate whether the changes were influenced by topical dorzolamide or the natural history.

Short-term high-fat feeding exacerbates degeneration in retinitis pigmentosa by promoting retinal oxidative stress and inflammation

2021 ◽  
Vol 118 (43) ◽  
pp. e2100566118
Author(s):  
Oksana Kutsyr ◽  
Agustina Noailles ◽  
Natalia Martínez-Gil ◽  
Lucía Maestre-Carballa ◽  
Manuel Martinez-Garcia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Retinitis Pigmentosa ◽  
Retinal Degeneration ◽  
Gut Microbiome ◽  
Cell Activation ◽  
High Fat ◽  
Short Term ◽  
Oxidative Markers ◽  
Degenerative Disorders ◽  
Inflammatory State

A high-fat diet (HFD) can induce hyperglycemia and metabolic syndromes that, in turn, can trigger visual impairment. To evaluate the acute effects of HFD feeding on retinal degeneration, we assessed retinal function and morphology, inflammatory state, oxidative stress, and gut microbiome in dystrophic retinal degeneration 10 (rd10) mice, a model of retinitis pigmentosa, fed an HFD for 2 to 3 wk. Short-term HFD feeding impaired retinal responsiveness and visual acuity and enhanced photoreceptor degeneration, microglial cell activation, and Müller cell gliosis. HFD consumption also triggered the expression of inflammatory and oxidative markers in rd10 retinas. Finally, an HFD caused gut microbiome dysbiosis, increasing the abundance of potentially proinflammatory bacteria. Thus, HFD feeding drives the pathological processes of retinal degeneration by promoting oxidative stress and activating inflammatory-related pathways. Our findings suggest that consumption of an HFD could accelerate the progression of the disease in patients with retinal degenerative disorders.

scholarly journals MODERN CONCEPTION AS TO THE FUNCTIONAL MORPHOLOGY OF THE OLFACTORY SYSTEM AND ITS CHANGES UNDER THE INFLUENCE OF SOME EXOGENOUS POLLUTANTS

2019 ◽  
Vol 23 (3-4) ◽  
pp. 37-40
Author(s):  
A.D. Shkodina ◽  
R.M. Hrinko ◽  
I.I. Starchenko
Keyword(s):  
Environmental Factors ◽  
Olfactory Epithelium ◽  
Functional Organization ◽  
Morphological Changes ◽  
Human Life ◽  
Experimental Studies ◽  
Experimental Models ◽  
Functional Changes ◽  
Olfactory Analyzer ◽  
Long Time

The interaction between a body and an environment provides the main aspects of human life. The study of the functional structure of the olfactory analyzer plays an important role both in clinical and in experimental studies, but the question of its features in humans needs detailed research. The paper presents the modern data of the structural and functional organization of the olfactory analyzer. Particular attention is paid to the structural organization of olfactory bulbs as most complicated and least studied component of the olfactory analyzer. The morphological and functional changes of the olfactory analyzer are developing in some diseases and in action of adverse environmental factors are described while the accentuation is placed on the differences of the mechanism in the pathogenesis of damage to the olfactory analyzer, depending on the nature of the influence of pathogenic factors. In this way as the result of short-term intense effects of the pollutant, irreversible atrophic changes are primarily affected to the olfactory epithelium, thus, to some extent, preventing the spread of the toxin to other analyzer structures. Conversely, a long-term exposure to low doses usually retains the functional activity of the olfactory epithelium, while harmful substances penetrate the central unit of the olfactory analyzer. In such cases, the olfactory dysfunction can be diagnosed after a long time after the start of the cohort with certain pollutants. Currently, studies of the influence of exogenous toxins on various parts of the olfactory analyzer on animal experimental models are quite active. At the same time, the issue of functional and morphological changes in various structural components of the human olfactory analyzer under the influence of negative environmental factors remains poorly understood and requires further morphological and biochemical studies, in order to be able to further develop effective therapeutic and prophylactic means.

scholarly journals The influence of the drug LHS-1208 on cardiovascular system

2018 ◽  
Vol 17 (3) ◽  
pp. 70-80
Author(s):  
N. P. Ermakova ◽  
I. V. Merkulova ◽  
O. I. Konyaeva ◽  
N. Yu. Kulbachevskaya ◽  
T. V. Abramova ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Total Dose ◽  
Cardiovascular System ◽  
Anticancer Drug ◽  
Aspartate Aminotransferase ◽  
Heart Muscle ◽  
Maximum Dose ◽  
Morphological Changes ◽  
Toxicological Study ◽  
Functional Changes

Introduction.This article presents a fragment of a preclinical toxicological study of a new Russian anticancer drug derived from n-glycoside indolokarbazole LCS-1208 – study of cardiotoxicity, which is one of the specific complications of anticancer chemotherapy.Objective.Preclinical toxicological study of the effect of the drug LCS-1208 on the cardiovascular system of animals to assess its cardiotoxic effects.Materials and methods.Studies were conducted on 40 healthy non-harmless mongrel male rats and 4 dogs Beagle, male and female. The drug was administered daily 15 times to rats-intraperitoneal in total doses of 50, 100 and 200 mg/kg; to dogs – intravenously in total doses of 20 and 30 mg/kg. The period of observation of rats was 30 days, for dogs was 60 days. Changes in electrocardiogram indices, macroscopic and histological picture of heart changes and changes in biochemical parameters of enzymes activity – lactate dehydrogenase and aspartate aminotransferase were evaluated.Results.In rats LCS-1208 throughout the period of observation caused functional changes in electrocardiogram: increase in PQ and QT intervals and cardiac rhythm disturbance (loss of R wave), which indicates a violation of electrical conductivity. Morphological changes in the heart muscle were detected on the 3rd day of observation in total doses of 100 and 200 mg/kg, which remained until 30 days of observation only in animals receiving the drug in the total dose of 200 mg/kg. In some dogs for different periods of observation the drug caused functional changes in the electrical activity of the heart: an increase in the QRS interval, the inversion of the T wave, the appearance of a deep Q wave and an increase in the activity of lactate dehydrogenase and aspartate aminotransferase compared to back ground indicators. Morphological changes in the heart muscle were detected on the 3rd day of observation only in the total dose of 30 mg/kg, which persisted up to 60 days of observation.Conclusion.It was found that the new Russian anticancer drug LHC-1208, a derivative of indocarbazole N-glycoside, has a cardiotoxic effect, causing functional changes in the cardiovascular system of rats in all doses studied, and in dogs only in the maximum dose. Morphologically, cardiotoxicity is not confirmed in animals receiving a minimal dose of the drug, but only in animals receiving the maximum dose of the drug.

Sign in / Sign up

Export Citation Format

Share Document