Ganglion Cell Density Research Articles

Inhibition of Retinal Ganglion Cell Loss By a Novel ROCK Inhibitor (E212) in Ischemic Optic Nerve Injury Via Antioxidative and Anti-Inflammatory Actions.

PurposeThis study investigated the neuroprotective effects of administration of ROCK inhibitor E212 on ischemic optic neuropathy.MethodsRats received an intravitreal injection of either E212 or PBS immediately after optic nerve infarct. The oxidative stress in the retina was detected by performing superoxide dismutase activity and CellROX assays. The integrity of retinal pigment epithelium was determined by staining of zona occludens 1. The visual function, retinal ganglion cell (RGC) density, and RGC apoptosis were determined by using flash visual-evoked potential analysis, retrograde FluoroGold labeling, and TdT-dUTP nick end-labeling assay. Macrophage infiltration was detected by staining for ED1. The protein levels of TNF-α, p-CRMP, p-AKT1, p-STAT3, and CD206 were evaluated using Western blotting.ResultsAdministration of E212 resulted in a 1.23-fold increase in the superoxide dismutase activity of the retina and 2.28-fold decrease in RGC-produced reactive oxygen species as compared to the levels observed upon treatment with PBS (P < 0.05). Moreover, E212 prevented the disruption of the blood-retinal barrier (BRB) in contrast to PBS. The P1-N2 amplitude and RGC density in the E212-treated group were 1.75- and 2.05-fold higher, respectively, than those in the PBS-treated group (P < 0.05). The numbers of apoptotic RGCs and macrophages were reduced by 2.93- and 2.54-fold, respectively, in the E212-treated group compared with those in the PBS-treated group (P < 0.05). The levels of p-AKT1, p-STAT3, and CD206 were increased, whereas those of p-PTEN, p-CRMP2, and TNF-α were decreased after treatment with E212 (P < 0.05).ConclusionsTreatment with E212 suppresses oxidative stress, BRB disruption, and neuroinflammation to protect the visual function in ischemic optic neuropathy.

Retinal Ganglion Counts in invasive Iguana iguana

Introduction Iguana iguana is an emerging invasive species in southeastern North America. To better understand their ability to outcompete native species for local resources, we investigate retina ganglion cell density in order to begin characterization visual acuity potential. Materials and Methods: We obtained four specimens from wildlife veterinarians culling invasive iguanas from southern Florida. Postmortem, we conducted whole globe enucleation, with special consideration to record globe orientation within the orbit. We performed retinal wholemounts and stained retinae for retinal ganglion cells with cresyl violet acetate. We photographed the retina at 100X and counted retinal ganglion cells in randomly generated areas using Image J. Cell counts were verified by three independent and blinded investigators. We generated a cell retina showing retinal ganglion cell density across the retina, indicating the position of the fovea. Results By combining the orientation of the retina within the globe and orbit and the map of retinal ganglion cell density, our results show a single macula and fovea that is located nasally approximately one optic disc diameter anterior to the optic disc, indicating that Iguana iguana has the highest visual acuity in the temporal visual field. Conclusion Retinal ganglion cell counts in Iguana iguana indicate a highly visual animal with good visual acuity. This may help us understand their success as an invasive species.

Visual function in guinea pigs: behavior and electrophysiology

ABSTRACT Clinical relevance Guinea pig visual function is characterised based on behavioural and electrophysiological measures and retinal ganglion cell density is examined to further develop the guinea pig as a model of human ocular conditions. Background Guinea pigs are an important model of human ocular conditions. Here, guinea pig spatial frequency discrimination, pattern and full-field photopic electroretinography (ERG), and retinal ganglion cell distribution were investigated. Methods Adult guinea pigs (n = 6) were included. Optomotor responses to square-wave gratings from 0.3 to 2.4 cycles per degree (cpd) were assessed. Pattern ERG responses were recorded using square-wave gratings from 0.025 to 0.25 cpd at 100% contrast, alternating at a temporal frequency of 1.05 Hz. Full-field ERG responses were recorded using a 10.0 cd.s/m2 flash. Ganglion cell density was determined histologically from retinal whole mounts. Results Maximum spatial frequency discrimination was 1.65 ± 0.49 cpd for stimuli rotating temporally to nasally and 0.75 ± 0.16 cpd for stimuli rotating nasally to temporally. For pattern ERG, a maximum amplitude of 3.50 ± 1.16 µV for the first negative to positive peak (N1P1) was elicited with a 0.025 cpd grating, and 2.5 ± 0.1 µV for the positive to second negative peak (P1N2) was elicited with a 0.05 cpd grating. For full-field ERG, a-wave amplitude was 19.2 ± 4.24 µV, b-wave amplitude was 33.6 ± 8.22 µV, and the PhNR was 24.0 ± 5.72 µV. Peak retinal ganglion cell density was 1621 ± 129 cells/mm2, located 1–2 mm superior to the optic nerve head. Conclusion Guinea pigs show directional selectivity for stimuli moving in the temporal to the nasal visual field. Guinea pigs demonstrate a quantifiable PhNR in the full-field ERG and negative and positive waveforms in the pattern ERG. The visual streak is located in the superior retina.

The Benefits and Hazards of Intravitreal Mesenchymal Stem Cell (MSC) Based-Therapies in the Experimental Ischemic Optic Neuropathy.

Mesenchymal stem cell (MSC) therapy has been investigated intensively for many years. However, there is a potential risk related to MSC applications in various cell niches. Methods: The safety of intravitreal MSC application and the efficacy of MSC-derived conditioned medium (MDCM) were evaluated in the normal eye and the diseased eye, respectively. For safety evaluation, the fundus morphology, visual function, retinal function, and histological changes of the retina were examined. For efficacy evaluation, the MDCM was intravitreally administrated in a rodent model of anterior ischemic optic neuropathy (rAION). The visual function, retinal ganglion cell (RGC) density, and neuroinflammation were evaluated at day 28 post-optic nerve (ON) infarct. Results: The fundus imaging showed that MSC transplantation induced retinal distortion and venous congestion. The visual function, retinal function, and RGC density were significantly decreased in MSC-treated eyes. MSC transplantation induced astrogliosis, microgliosis, and macrophage infiltration in the retina due to an increase in the HLA-DR-positive MSC proportion in vitreous. Treatment with the MDCM preserved the visual function and RGC density in rAION via inhibition of macrophage infiltration and RGC apoptosis. Conclusions: The vitreous induced the HLA-DR expression in the MSCs to cause retinal inflammation and retina injury. However, the MDCM provided the neuroprotective effects in rAION.

Effect of Resveratrol in Expression of Caspase-7 and Retinal Ganglion Cells in a Rat Model With Traumatic Optic Neuropathy

Objective: To analize the effect of resveratrol to the expression of caspase-7 and density of retinal ganglioncells in a rat model with Traumatic Optic Neuropathy (TON) compared to control.Methods: This is an experimental study using Wistar rats. Samples were divided into four groups. Onenormal control group, 1 TON control group and 2 TON resveratrol groups. TON induced by clamping theoptic nerve retrobulbar with Hartmann Mosquito 2,5 inch. Resveratrol was given 10 mg/Kg and 20 mg/Kgin two resveratrol groups. Enucleation was performed 1 day after to evaluate the expression of Caspase-7 byimmunohistochemistry and density of retinal ganglion cell by hematoxicilin eosin staining.Results: Caspase-7 expression was lowest in the resveratrol 20 mg/kg treatment group (4.00 ± 2.00)compared to resveratrol 10 mg/kg treatment group (6.00±2.23), TON control group(6.00 ± 6.78) and normalcontrol group(7.20 ± 2.58). Retinal ganglion cell density was highest in the resveratrol 10 mg/kg treatmentgroup (27.23±2.75) compared to resveratrol 20 mg/kg treatment group (24.89±5.83), normal controlgroup(24.19±2.39) and the lowest in TON control group (22.96±4.62). Based on the Pearson correlation test,it was found that there was no correlation between Caspase-7 expression and retinal ganglion cell density ina rat model with TON (p: 0.178; r = 0.314)Conclusions: Resveratrol administration shows effect in lowering apoptosis marker caspase-7 and preservingretinal ganglion cell in traumatic optic neuropathy.

The Relationship Between Macula Retinal Ganglion Cell Density and Visual Function in the Nonhuman Primate.

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.

GanglionNet: Objectively assess the density and distribution of ganglion cells with NABLA-N network

Abstract Hirschsprung's disease (HD) is a birth defect which is diagnosed and managed by multiple medical specialties such as pediatric gastroenterology, surgery, radiology, and pathology. HD is characterized by absence of ganglion cells in the distal intestinal tract with a gradual normalization of ganglion cell numbers in adjacent upstream bowel, termed the transition zone (TZ). Definitive surgical management to remove the abnormal bowel requires accurate assessment of ganglion cell density in histological sections from the TZ, which is difficult, time-consuming and prone to operator error. We present an automated method to detect and count immunostained ganglion cells using a new NABLA-N network-based deep learning (DL) approach, called “GanglionNet”. The morphological image analysis methods are applied for refinement of the regions for counting of the cells and define ganglia regions (a set of ganglion cells) from the predicted masks. The proposed model is trained with single point annotated samples by the expert pathologist. The GanglionNet is tested on ten completely new High-Power Field (HPF) images with dimension of 2560 × 1920 pixels and the outputs are compared against the manual counting results by the expert pathologist. The proposed method shows a robust 97.49% detection accuracy for ganglion cells, when compared to counts by the expert pathologist, which demonstrates the robustness of GanglionNet. The proposed DL-based ganglion cell detection and counting method will simplify and standardize TZ diagnosis for HD patients.

ТОПОГРАФИЯ ГАНГЛИОЗНОГО СЛОЯ СЕТЧАТКИ И РЕТИНАЛЬНОЕ РАЗРЕШЕНИЕ У ГРЕБНЕЗУБОГО ДЕЛЬФИНА STENO BREDANENSIS (CETACEA: DELPHINIDAE)

Morphological investigation of the retinal ganglion layer in the rough-toothed dolphin Steno bredanensis was performed using the retinal wholemount technique. Mapping of the distribution density of ganglion cells revealed two areas of their concentration: in the nasal (544 cells/mm2) and temporal (594 cells/mm2) quadrants. Ganglion cell diameters ranged from 12 to 50 µm, with mean values varying from 20 to 29 µm in different areas. The obtained cell distribution density corresponded to a retinal resolution of 11’

Soft hydrogel promotes dorsal root ganglion by upregulating gene expression of Ntn4 and Unc5B

Mechanical property is an important factor of cellular microenvironment for neural tissue regeneration. In this study, polyacrylamide (PAM) hydrogels with systematically varying elastic modulus were prepared using in situ radical polymerization. We found that the hydrogel was biocompatible, and the length of dorsal root ganglion (DRG)'s axon and cell density were optimal on the hydrogels with elastic modulus of 5.1 kPa (among hydrogels with elastic modulus between 3.6 kPa and 16.5 kPa). These DRGs also exhibited highest gene and protein expression of proliferation marker Epha4, Ntn4, Sema3D and differentiation marker Unc5B. Our study revealed the mechanism of how material stiffness affects DRG proliferation and differentiation. It will also provide theoretical basis and evidence for the design and development of nerve graft with better repair performance.

Investigation of associations between Piezo1 mechanoreceptor gain-of-function variants and glaucoma-related phenotypes in humans and mice

Glaucoma disproportionately affects individuals of African descent. Prior studies of the PIEZO1 mechanoreceptor have suggested a possible role in glaucoma pathophysiology. Here, we investigated associations between a Piezo1 gain-of-function variant common in individuals of African descent with glaucoma-related phenotypes. We analyzed whole genome sequences to identify Piezo1 variants and their frequencies among 1565 human participants. For the most common variant (e756del), we compared phenotypes between heterozygotes, homozygotes, and wildtypes. Longitudinal mixed effects models of visual field mean deviation (MD) and retinal nerve fiber layer (RNFL) thickness were used to evaluate progression. Based on trends in the models, further investigation was conducted using Piezo1 gain-of-function mice. About 30% of African descent individuals had at least one e756del allele. There were trends suggesting e756del was associated with higher IOPs, thinner RNFLs, lower optic nerve head capillary densities, and greater decreases in MD and RNFL thickness over time, but these did not reach statistical significance. Among mice, increased Piezo1 activity was not significantly associated with IOP or retinal ganglion cell density. Our study confirms that the Piezo1 e756del gain-of-function variant is a frequent polymorphism present in African descent individuals but is unrelated to examined differences in glaucoma phenotypes. Ongoing work is needed to elucidate the role of Piezo1-mediated mechanotransduction in glaucoma.

Comparative retinal histomorphometry and visual acuity of three bat species of the genus Artibeus (Phyllostomidae: Stenodermatinae)

ABSTRACT: This study performed a histomorphometric analysis of the retina and estimated the visual acuity of three fruit-eating bats of the genus Artibeus, including Artibeus lituratus, Artibeus planirostris and Artibeus obscurus. In total, 13 animals were used for this study, in which the retinas were hemidisected, fixed, cut, and stained. The visual acuity was determined by the density of ganglion cells in the retina and the retinal layers were also measured from histological sections. The retinas of these bats are avascular, do not present tapetum lucidum in any quadrant, and have the 10 retinal layers common in mammals. Moreover, it was observed that the thickness of the retina in the central region was significantly higher in all measured parameters (p&lt;0.001), except for the outer plexiform layer (OPL) which was significantly higher in the peripheral region (p&lt;0.001). The retinas of the three species showed a horizontal visual streak with a higher concentration of retinal ganglion cells (RGCs) at the inferotemporal region. In addition, the species A. lituratus exhibited extras areas of high cell density in the retina. Thus, A. lituratus showed the highest visual acuity (1.92 cycles/degree), while A. planirostris showed a visual acuity of (1.77 cycles/degree) and A. obscurus exhibited the lowest visual acuity (1.50 cycles/degree). All these characteristics are related to the echolocation system and the eating habits of each species. Therefore, it can be concluded that bats of the genus Artibeus have a high visual acuity value compared to other echolocating bats and all these differences might be directly linked to the phylogeny of the genus.

Retinal ganglion cell ablation in guinea pigs

Guinea pigs are a common model of human ocular conditions; however, their visual function has not been fully characterized. The purpose of this study was to determine the contributions of retinal ganglion cells to structural and functional measures in guinea pigs. Healthy adult guinea pigs (n = 12) underwent unilateral optic nerve crush. Retinal structure was assessed with spectral domain optical coherence tomography (OCT), and thickness of the ganglion cell/nerve fiber layer (GC/NFL) was determined. Visual function was assessed with optomotor tracking of a drifting grating and light adapted electroretinograms (ERGs). From flash ERGs, a-wave, b-wave, oscillatory potentials (OPs), and photopic negative response (PhNR) were analyzed. From pattern ERGs, N1P1 and P1N2 were analyzed. Histological studies were done at various time points for ganglion cell quantification. Optomotor tracking was absent in optic nerve crush eyes following optic nerve crush. Significant thinning of the GC/NFL was evident four weeks following the crush. Flash ERGs revealed a significant reduction in the OP1 amplitude two weeks following crush (P < 0.01) and in the PhNR amplitude six weeks following crush (P < 0.01). There were no significant changes in a-wave, b-wave, or pattern ERG responses (P > 0.05 for all). In vivo OCT imaging showed progressive thinning of inner retinal layers. Ganglion cell density, quantified histologically, was significantly reduced by 75% in the optic nerve crush eye compared to the control eye at four weeks following crush. These findings indicate that retinal ganglion cells contribute to the PhNR and OP1 components of the full field flash ERG, but not significantly to the pattern ERG in guinea pigs. This study demonstrates that OCT imaging and full field flash ERGs are valuable in assessing retinal ganglion cell loss in vivo in guinea pigs and will help to further establish the guinea pig as a model of human ocular pathologies.

Retinal ganglion cell topography and spatial resolution in the Japanese smelt Hypomesus nipponensis (McAllister, 1963).

Vision plays a crucial role in the life of the vast majority of vertebrate species. The spatial arrangement of retinal ganglion cells has been reported to be related to a species' visual behavior. There are many studies focusing on the ganglion cell topography in bony fish species. However, there are still large gaps in our knowledge on the subject. We studied the topography of retinal ganglion cells (GCs) in the Japanese smelt Hypomesus nipponensis, a highly visual teleostean fish with a complex life cycle. DAPI labeling was used to visualize cell nuclei in the ganglion cell and inner plexiform layers. The ganglion cell layer was relatively thin (about 6-8μm), even in areas of increased cell density (area retinae temporalis), and was normally composed of a single layer of cells. In all retinal regions, rare cells occurred in the inner plexiform layer. Nissl-stained retinae were used to estimate the proportion of displaced amacrine cells and glia in different retinal regions. In all retinal regions, about 84.5% of cells in the GC layer were found to be ganglion cells. The density of GCs varied across the retina in a regular way. It was minimum (3990 and 2380 cells/mm2 in the smaller and larger fish, respectively) in the dorsal and ventral periphery. It gradually increased centripetally and reached a maximum of 14,275 and 10,960 cells/mm2 (in the smaller and larger fish, respectively) in the temporal retina, where a pronounced area retinae temporalis was detected. The total number of GCs varied from 177×103 (smaller fish) to 212×103 cells (larger fish). The theoretical anatomical spatial resolution (the anatomical estimate of the upper limit of visual acuity calculated from the density of GCs and eye geometry and expressed in cycles per degree) was minimum in the ventral periphery (smaller fish, 1.46cpd; larger fish, 1.26cpd) and maximum in area retinae temporalis (smaller fish, 2.83cpd; larger fish, 2.75cpd). The relatively high density of GCs and the presence of area retinae temporalis in the Japanese smelt are consistent with its highly visual behavior. The present findings contribute to our understanding of the factors affecting the topography of retinal ganglion cells and visual acuity in fish.

Analysis of Parvocellular and Magnocellular Visual Pathways in Human Retina.

Two main subcortical pathways serving conscious visual perception are the midget-parvocellular (P), and the parasol-magnocellular (M) pathways. It is generally accepted that the P pathway serves red-green color vision, but the relative contribution of P and M pathways to spatial vision is a long-standing and unresolved issue. Here, we mapped the spatial sampling properties of P and M pathways across the human retina. Data were obtained from immunolabeled vertical sections of six postmortem male and female human donor retinas and imaged using high-resolution microscopy. Cone photoreceptors, OFF-midget bipolar cells (P pathway), OFF-diffuse bipolar (DB) types DB3a and DB3b (M pathway), and ganglion cells were counted along the temporal horizontal meridian, taking foveal spatial distortions (postreceptoral displacements) into account. We found that the density of OFF-midget bipolar and OFF-midget ganglion cells can support one-to-one connections to 1.05-mm (3.6°) eccentricity. One-to-one connections of cones to OFF-midget bipolar cells are present to at least 10-mm (35°) eccentricity. The OFF-midget ganglion cell array acuity is well-matched to photopic spatial acuity measures throughout the central 35°, but the OFF-parasol array acuity is well below photopic spatial acuity, supporting the view that the P pathway underlies high-acuity spatial vision. Outside the fovea, array acuity of both OFF-midget and OFF-DB cells exceeds psychophysical measures of photopic spatial acuity. We conclude that parasol and midget pathway bipolar cells deliver high-acuity spatial signals to the inner plexiform layer, but outside the fovea, this spatial resolution is lost at the level of ganglion cells.SIGNIFICANCE STATEMENT We make accurate maps of the spatial density and distribution of neurons in the human retina to aid in understanding human spatial vision, interpretation of diagnostic tests, and the implementation of therapies for retinal diseases. Here, we map neurons involved with the midget-parvocellular (P pathway) and parasol-magnocellular (M pathway) through human retina. We find that P-type bipolar cells outnumber M-type bipolar cells at all eccentricities. We show that cone photoreceptors and P-type pathway bipolar cells are tightly connected throughout the retina, but that spatial resolution is lost at the level of the ganglion cells. Overall, the results support the view that the P pathway is specialized to serve both high acuity vision and red-green color vision.

Ganglion cells and displaced amacrine cells density in the retina of the collared peccary (Pecari tajacu).

In the present study, we investigated the topographical distribution of ganglion cells and displaced amacrine cells in the retina of the collared peccary (Pecari tajacu), a diurnal neotropical mammal of the suborder Suina (Order Artiodactyla) widely distributed across central and mainly South America. Retinas were prepared and processed following the Nissl staining method. The number and distribution of retinal ganglion cells and displaced amacrine cells were determined in six flat-mounted retinas from three animals. The average density of ganglion cells was 351.822 ± 31.434 GC/mm2. The peccary shows a well-developed visual streak. The average peak density was 6,767 GC/mm2 and located within the visual range and displaced temporally as an area temporalis. Displaced amacrine cells have an average density of 300 DAC/mm2, but the density was not homogeneous along the retina, closer to the center of the retina the number of cells decreases and when approaching the periphery the density increases, in addition, amacrine cells do not form retinal specialization like ganglion cells. Outside the area temporalis, amacrine cells reach up to 80% in the ganglion cell layer. However, in the region of the area temporalis, the proportion of amacrine cells drops to 32%. Thus, three retinal specializations were found in peccary’s retina by ganglion cells: visual streak, area temporalis and dorsotemporal extension. The topography of the ganglion cells layer in the retina of the peccary resembles other species of Order Artiodactyla already described and is directly related to its evolutionary history and ecology of the species.

Blue-yellow deficiencies in young moderate smokers

PurposeTo evaluate whether tobacco affects color vision in young moderate smokers. MethodsChromatic mechanisms of 13 moderate smokers (10–20 cigarettes/day and at least 5 years smoking) and 17 non-smokers in the 18–35 age range were assessed with the Farnsworth-Munsell 100-hue (FM100h) test and short wavelength automated perimetry (SWAP). ResultsFM100h Total Error Scores (TES) were higher for smokers, and although differences were not significant (p = 0.14), a linear model with principal component analysis was able to explain 95% of the variance in TES and red-green partial error scores, though not in blue-yellow partial error scores (p = 0.07), using the number of years as smokers and the number of cigarettes/day as predictors. SWAP sensitivity values were globally worse (p = 0.002) for smokers (25.7 + 6.2 dB) than for non-smokers (26.7 + 6.2 dB). In the upper visual hemifield sensitivity, total deviation and pattern deviation values were worse for smokers (p < 0.001). Differences in mean defect and pattern standard deviation were not significant (p > 0.05 in both cases). The number of out-of-limits points in the total difference and pattern difference map were significantly larger for smokers. After correcting for multiple comparisons, only the differences in the upper visual hemifield were significant. ConclusionsThis pilot study suggests that even young moderate smokers show small sensitivity loss in the blue-yellow mechanism, it is statistically significant, restricted to the upper visual hemifield. This corresponds to a retinal region where literature reports a lower density of retinal ganglion cells and where, therefore, the chromatic mechanisms would be more fragile.

Evaluation of Nivolumab for Ototoxic Effects: An Animal Study in Rats.

The aim of this study was to assess whether nivolumab is ototoxic in rats and whether this ototoxicity is dose-dependent. Twelve rats were divided into two groups: Group 1 (control group, 6 rats, 12 ears) received intraperitoneal saline for 14 days. Group 2 (study group, 6 rats, 12 ears) and received two doses of 3 mg/kg intraperitoneal nivolumab within 14 days. Auditory brainstem responses (ABRs) were performed preoperatively and 4 and 8 weeks postoperatively. We compared between the groups, morphologic appearance of spiral ganglion cells and organ of Corti and density of spiral ganglion cells (measured with conventional light microscope connected to a personal computer). In our control group, both spiral ganglion and organ of corti had a normal morphological appearance. In our study group, spiral ganglion cells had a normal morphological appearance. However, some sections showed possibly mild degenerative changes in the organ of corti. Of 12 samples in the study group, four had a significant loss of density of spiral ganglion cells compared to the control group. The baseline ABR thresholds did not significantly differ between the groups (p=0.713). There was no statistically significant difference between the groups regarding ABR thresholds at week 4 (p=0.347). However, a statistically significant difference was observed in the ABR thresholds at week 8 (p=0.045). The results of our study showed that nivolumab treatment has ototoxic effects. Based on our results, we recommend monitoring the changes in the hearing ability of chemotherapy patients.

Amphibious vision – Optical design model of the hooded merganser eye

A comprehensive schematic eye model of the hooded merganser is introduced for the first time to advance the understanding of amphibious vision. It is comprised of two different configurations, the first one modeling its visual system in air (unaccommodated state) and the second one representing the case where the eye is immersed in water (accommodated state). The model was designed using available data of former studies, image analysis and the implementation of feasible assumptions that serve as starting values. An optimization process incorporating an optical design program is used to vary the starting values with the aim of finding the setup offering the best acuity. The image quality was measured using the root-mean-square radius of the focal spot formed on the retina. The resulting schematic eye model comprises all relevant optical specifications, including aspherical geometrical parameters for cornea and lens, distances between the surfaces, the gradient index distribution of the lens, the retinal specifications and the object distance in both media. It achieves a spot radius of 4.20 μm for the unaccommodated state, which meets the expectations derived by the mean ganglion cell density and comparison with other animals. In contrast, under water the determined spot radius of 11.48 µm indicates an acuity loss. As well as enhancing our understanding of the vision of the hooded merganser, the schematic eye model may also serve as a simulation basis for examing similar animal eyes, such as the cormorant or other fish hunting birds.

Altered spatial summation optimizes visual function in axial myopia

This study demonstrates significant differences between the area of complete spatial summation (Ricco’s area, RA) in eyes with and without non-pathological, axial myopia. Contrast thresholds were measured for six stimuli (0.01–2.07 deg2) presented at 10º eccentricity in 24 myopic subjects and 20 age-similar non-myopic controls, with RA estimated using iterative two-phase regression analysis. To explore the effects of axial length-induced variations in retinal image size (RIS) on the measurement of RA, refractive error was separately corrected with (i) trial lenses at the anterior focal point (near constant inter-participant RIS in mm), and (ii) contact lenses (RIS changed with axial length). For spectacle corrected measurements, RA was significantly larger in the myopic group, with a significant positive correlation also being observed between RA and measures of co-localised peripheral ocular length. With contact lens correction, there was no significant difference in RA between the groups and no relationship with peripheral ocular length. The results suggest RA changes with axial elongation in myopia to compensate for reduced retinal ganglion cell density. Furthermore, as these changes are only observed when axial length induced variations in RIS are accounted for, they may reflect a functional adaptation of the axially-myopic visual system to an enlarged RIS.

Systemic Mesenchymal Stem Cell Treatment Mitigates Structural and Functional Retinal Ganglion Cell Degeneration in a Mouse Model of Multiple Sclerosis.

PurposeThe purpose of this study was to determine mesenchymal stem cell (MSC) therapy efficacy on rescuing the visual system in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS) and to provide new mechanistic insights.MethodsEAE was induced in female C57BL6 mice by immunization with myelin oligodendrocyte glycoprotein (MOG)35–55, complete Freund's adjuvant, and pertussis toxin. The findings were compared to sham-immunized mice. Half of the EAE mice received intraperitoneally delivered stem cells (EAE + MSC). Clinical progression was monitored according to a five-point EAE scoring scheme. Pattern electroretinogram (PERG) and retinal nerve fiber layer (RNFL) thickness were measured 32 days after induction. Retinas were harvested to determine retinal ganglion cell (RGC) density and prepared for RNA-sequencing.ResultsEAE animals that received MSC treatment seven days after EAE induction showed significantly lower motor-sensory impairment, improvement in the PERG amplitude, and preserved RNFL. Analysis of RNA-sequencing data demonstrated statistically significant differences in gene expression in the retina of MSC-treated EAE mice. Differentially expressed genes were enriched for pathways involved in endoplasmic reticulum stress, endothelial cell differentiation, HIF-1 signaling, and cholesterol transport in the MSC-treated EAE group.ConclusionsSystemic MSC treatment positively affects RGC function and survival in EAE mice. Better cholesterol handling by increased expression of Abca1, the cholesterol efflux regulatory protein, paired with the resolution of HIF-1 signaling activation might explain the improvements seen in PERG of EAE animals after MSC treatment.Translational RelevanceUsing MSC therapy in a mouse model of MS, we discovered previously unappreciated biochemical pathways associated with RGC neuroprotection, which have the potential to be pharmacologically targeted as a new treatment regimen.