Structure-Function Relationship of Retinal Ganglion Cells in Multiple Sclerosis.
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ABSTRACT:
SUBMITTER: Al-Nosairy KO
PROVIDER: S-EPMC8037992 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:A subpopulation of retinal ganglion cells (RGCs) expresses the photopigment melanopsin, rendering these cells intrinsically photosensitive (ipRGCs). These cells are critical for competent circadian entrainment, pupillary light reflex, and other non-imaging-forming photic responses. Research has now demonstrated the presence of multiple subpopulations of ipRGC based on the dendritic stratification in the inner plexiform layer (IPL), those monostratified in the Off sublamina (M1), those monostratified in the On sublamina (M2,4,5), and those bistratified in both the On and the Off sublaminae (M3). Despite evidence that M1 and M2 cells are distinct subpopulations of ipRGC based on distinct morphological and physiological properties, the inclusion of M3 cells as a distinct subtype has remained controversial. Aside from the identification of M3 cells as a morphological subpopulation of ipRGC, to date there have been no functional descriptions of M3 cell physiology or synaptic inputs. Our data provide the first in-depth description of M3 cell structural and functional properties. We report that M3 cells form a morphologically heterogeneous population but one that is physiologically homogeneous with properties similar to those of M2 cells.
| S-EPMC3714856 | biostudies-literature
Project description:Human Müller glia with stem cell characteristics (hMGSCs) have been shown to improve retinal function upon transplantation into rat models of retinal ganglion cell (RGC) depletion. However, their translational potential may depend upon successful engraftment and improvement of retinal function in experimental models with anatomical and functional features resembling those of the human eye. We investigated the effect of allogeneic transplantation of feline Müller glia with the ability to differentiate into cells expressing RGC markers, following ablation of RGCs by N-methyl-d-aspartate (NMDA). Unlike previous observations in the rat, transplantation of hMGSC-derived RGCs into the feline vitreous formed aggregates and elicited a severe inflammatory response without improving visual function. In contrast, allogeneic transplantation of feline MGSC (fMGSC)-derived RGCs into the vitrectomized eye improved the scotopic threshold response (STR) of the electroretinogram (ERG). Despite causing functional improvement, the cells did not attach onto the retina and formed aggregates on peripheral vitreous remnants, suggesting that vitreous may constitute a barrier for cell attachment onto the retina. This was confirmed by observations that cellular scaffolds of compressed collagen and enriched preparations of fMGSC-derived RGCs facilitated cell attachment. Although cells did not migrate into the RGC layer or the optic nerve, they significantly improved the STR and the photopic negative response of the ERG, indicative of increased RGC function. These results suggest that MGSCs have a neuroprotective ability that promotes partial recovery of impaired RGC function and indicate that cell attachment onto the retina may be necessary for transplanted cells to confer neuroprotection to the retina. Significance: Müller glia with stem cell characteristics are present in the adult human retina, but they do not have regenerative ability. These cells, however, have potential for development of cell therapies to treat retinal disease. Using a feline model of retinal ganglion cell (RGC) depletion, cell grafting methods to improve RGC function have been developed. Using cellular scaffolds, allogeneic transplantation of Müller glia-derived RGC promoted cell attachment onto the retina and enhanced retinal function, as judged by improvement of the photopic negative and scotopic threshold responses of the electroretinogram. The results suggest that the improvement of RGC function observed may be ascribed to the neuroprotective ability of these cells and indicate that attachment of the transplanted cells onto the retina is required to promote effective neuroprotection.
| S-EPMC4729554 | biostudies-literature
Project description:This study tested whether repeated traumatic brain injuries (TBIs) alter the objective structure or the objective function of retinal ganglion cells (RGCs) in human subjects recruited from an optometry clinic. Case subjects (n = 25) with a history of repeated TBIs (4.12 ± 2.76 TBIs over 0-41 years) and healthy pair-matched control subjects (n = 30) were prospectively recruited. Retinal nerve fiber layer (RNFL) thickness was quantified with spectral-domain optical coherence tomography, and scanning laser polarimetry measured RNFL phase retardation. Measurements of the photopic negative response were made using full-field flash electroretinography. There was no statistically significant difference (p = 0.42) in global RNFL thickness between the case cohort (96.6 ± 9.4 microns) and the control cohort (94.9 ± 7.0 microns). There was no statistically significant difference (p = 0.80) in global RNFL phase retardation between the case cohort (57.9 ± 5.7 nm) and the control cohort (58.2 ± 4.6 nm). There were no statistically significant differences in the peak time (p = 0.95) of the PhNR or in the amplitude (p = 0.11) of the PhNR between the case cohort (69.9 ± 6.9 ms and 24.1 ± 5.1 μV, respectively) and the control cohort (70.1 ± 8.9 ms and 27.8 ± 9.1 μV, respectively). However, PhNR amplitude was more variable (p < 0.025) in the control cohort than in the case cohort. Within the case cohort, there was a strong positive (r = 0.53), but not statistically significant (p = 0.02), association between time since last TBI and PhNR amplitude. There was also a modest positive (r = 0.45), but not statistically significant (p = 0.04), association between time since first TBI and PhNR amplitude. Our results suggest that there were no statistically significant differences in the objective structure or in the objective function of RGCs between the case cohort and the control cohort. Future large, longitudinal studies will be necessary to confirm our negative results and to more fully investigate the potential interaction between PhNR amplitude and time since first or last TBI.
| S-EPMC9412167 | biostudies-literature
Project description:AimTo evaluate structural changes in the retina and their correlation with visual dysfunction in patients with multiple sclerosis.MethodsPatients with multiple sclerosis (n = 84) and healthy controls (n = 84) underwent structural evaluation of the retinal nerve fiber layer, and macular and ganglion cell layer thicknesses using Spectral domain optical coherence tomography (SD-OCT). All subjects underwent high and low contrast visual acuity, color vision (using the Farnsworth and L´Anthony desaturated D15 color tests), and contrast sensitivity vision using the Pelli Robson chart and CSV 1000E test.ResultsMacular, retinal nerve fiber layer, and ganglion cell layer thinning was observed in multiple sclerosis patients compared to healthy controls (p<0.05). High- and low-contrast visual acuity and contrast sensitivity vision at four different spatial frequencies were significantly reduced in comparison with healthy subjects (p<0.05). Macular, retinal nerve fiber layer and ganglion cell layer measurements correlated with high and low contrast visual acuity, and contrast sensitivity vision. Contrast sensitivity vision was the functional parameter that most strongly correlated with the structural measurements in multiple sclerosis and was associated with ganglion cell layer measurements. The L´Anthony color vision score (age-corrected color confusion index) was associated with macular measurements.ConclusionsPatients with multiple sclerosis had visual dysfunction that correlated with structural changes evaluated by SD-OCT. Macular and ganglion cell layer measurements may be good indicators of visual impairment in multiple sclerosis patients.
| S-EPMC4924797 | biostudies-literature
Project description:Retinal ganglion cell degeneration underlies several conditions which give rise to significant visual compromise, including glaucoma, hereditary optic neuropathies, ischaemic optic neuropathies, and demyelinating disease. In this review, we discuss the emerging strategies for neuroprotection specifically in the context of glaucoma, including pharmacological neuroprotection, mesenchymal stem cells, and gene therapy approaches. We highlight potential pitfalls that need to be considered when developing these strategies and outline future directions, including the prospects for clinical trials.
| S-EPMC5306473 | biostudies-other
Project description:PurposeLoss of ganglion cell inner plexiform layer (GCIPL) and visual sensitivity in the macula region are known to occur at all stages of glaucoma. While both are dependent on the underlying retinal ganglion cells (RGCs), the relationship between structure and function is modest. We hypothesize that the imprecise relationship is due to a lack of direct correspondence between in vivo measures and RGC counts, as well as the relatively large stimulus size used by standard perimetry, which exceeds spatial summation.MethodsThe relationship between optical coherence tomography (OCT)-derived GCIPL thickness and corresponding inner cell density from retinal flat mounts was determined for four nonhuman primates with varying stages of neuropathy. Normative data for 10-2 threshold using Goldman size I to V stimuli were established for 10 animals, 4 of which were then followed longitudinally with OCT and perimetry. The relationship between GCIPL volume, which incorporated stimulus size after removal of residual thickness, and differential light sensitivity was determined for both experimental glaucoma and healthy eyes.ResultsPeak inner retinal cell density was 63,052 ± 9238 cells/mm2 in the healthy eye. Cell density was related to both GCIPL thickness and eccentricity (R2 = 0.74, P < .01). For all 10-2 eccentricities, size III stimuli were greater than the critical area (P < 0.01). Based on the structural and histologic relationship, the critical area corresponds to approximately 156 RGCs.ConclusionsThe relationship between cell density and GCIPL thickness is dependent on retinal eccentricity. For 10-2 perimetry, perimetric loss, especially at earlier stages of neuropathy, may best be detected using size II or smaller stimuli.
| S-EPMC7794274 | biostudies-literature
Project description: Not available
| S-EPMC6905337 | biostudies-literature
Project description:BackgroundMelanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGC) area third class of photoreceptors in the retina in addition to rods and cones. They are a small heterogeneous population of cells primarily mediating non-image-forming visual functions.ObjectiveThis article provides an overview of the current understanding of the functions and the diversity of ipRGCs. It moreover gives an insight into clinically and translationally relevant aspects and treatment options.Material and methodsNarrative review article.ResultsipRGCs make up ~1-2% of all retinal ganglion cells and are divided into 6 specialized subtypes. With the photopigment melanopsin they can trigger light responses without rod or cone input and can relay irradiance information to various centers of the brain. Depending on the subtype, ipRGCs mediate non-image-forming tasks, such as the pupillary light reflex or synchronizing the circadian clock, and image-forming tasks, such as contrast optimization. ipRGCs exhibit differential resilience against optic nerve damage, making them an interesting study object for the development of neuroprotective strategies. In addition, melanopsin is an attractive optogenetic tool for vision restoration.ConclusionKnowledge on ipRGC physiology is indispensable for understanding frequent clinical observations. Their functional and morphological features are the subject of active research, which highlights novel translational strategies.
| S-EPMC9005408 | biostudies-literature
Project description:PurposeTo investigate the relationship between cup-to-disc ratio (CDR) and estimates of retinal ganglion cell (RGC) number.MethodsThis cross-sectional study included 156 healthy eyes, 53 glaucoma suspects, and 127 eyes with glaucoma. All eyes had standard automated perimetry (SAP), Cirrus SD-OCT, and stereoscopic optic disc photography within 6 months. CDR was determined from stereoscopic photographs by two or more masked graders. The number of RGCs in each eye was estimated using a published model that combines estimates of RGC number from SAP sensitivity thresholds and SD-OCT retinal nerve fiber layer measurements.ResultsThe mean estimated RGC count was 1,063,809 in healthy eyes; 828,522 in eyes with suspected glaucoma; and 774,200 in early, 468,568 in moderate, and 218,471 in advanced glaucoma. Healthy eyes had a mean vertical CDR of 0.45 ± 0.15 vs. 0.80 ± 0.16 in glaucomatous eyes. There was good correlation between stereophotographic vertical CDR and SD-OCT vertical CDR (R(2) = 0.825; P < 0.001). The relationship between estimated RGCs and vertical CDR was best represented using a third degree polynomial regression model, including age and optic disc area, which accounted for 83.3% of the variation in estimated RGC counts. The nonlinear relationship between RGC estimates and CDRs indicated that eyes with a large CDR would require loss of large RGC numbers for a small increase in CDR.ConclusionsThe relationship between estimated RGC counts and CDR suggests that assessment of change in CDR is an insensitive method for evaluation of progressive neural losses in glaucoma. Even relatively small changes in CDR may be associated with large losses of RGCs, especially in eyes with large CDRs. (ClinicalTrials.gov numbers, NCT00221923, NCT00221897.).
| S-EPMC3648225 | biostudies-literature
Project description:AIM:In glaucoma, depression and disturbed sleep has been associated with degeneration of the intrinsically photosensitive retinal ganglion cells, that mediate non-image forming effects of light such as regulation of circadian rhythm, alertness and mood. In this study we assessed associations between seasonal mood and behavior variation and retinal ganglion cell damage in outpatients with glaucoma. METHODS:The seasonal pattern assessment questionnaire was administered to outpatients with glaucoma. Data on visual field defects identified by autoperimetry and retinal nerve fiber layer thickness visualized by ocular coherence tomography were collected from patient charts. The correlations between seasonality and retinal damage were tested and the adjusted effects of retinal function on seasonality were evaluated in a linear regression model. RESULTS:In total, 113 persons completed the questionnaire. Of these, 4% fulfilled the criteria for seasonal affective disorder (SAD) and 8% for subsyndromal seasonal affective disorder (sSAD). Mean global seasonal score was 4.3. There were no significant correlations between seasonality and either visual field or retinal nerve fiber layer thickness. In the adjusted analysis there were trends toward differential effects of visual field on seasonality in subgroups with different sex and type of glaucoma. CONCLUSION:There were no strong associations between seasonality and visual field or retinal nerve fiber layer thickness. Sex, age and glaucoma subtype may modify light effects on complex regulatory systems.
| S-EPMC7067444 | biostudies-literature