Search Results (43)

Objectives: Insulin plays a crucial role in neuronal survival and oxidative stress modulation, making it a potential therapeutic target. This study investigates the effects of insulin in combination with a mesenchymal cell-derived secretome in patients with degenerative neuroretinal diseases. Methods: Sixty-four patients with severe neuroretinal diseases who had previously undergone the Limoli Retinal Restoration Technique (LRRT) were included in this longitudinal study and divided into groups: group 1 received a single injection of 5 units of insulin lispro into the suprachoroidal space of the worse-seeing eye; group 2 received insulin injection in the better-seeing eye. Retinal function was assessed using microperimetry (MY) before and after treatment (approximately 1 year for eye drops). Group 3 consisted of patients who demonstrated improvement in MY after insulin injection. These patients continued treatment with daily insulin eye drops. Results: In group 1, insulin-treated eyes showed a significant increase in retinal sensitivity from 10.09 dB to 10.75 dB (p = 0.0067), while untreated eyes declined from 12.35 dB to 11.92 dB (p = 0.0448). In group 2, insulin-treated eyes improved from 10.8 dB to 11.63 dB (p = 0.05), whereas untreated eyes exhibited a decline from 8.68 dB to 8.50 dB (p = 0.6771). In group 3, patients using insulin eye drops showed a stabilization or mild increase in retinal sensitivity, from 11.39 dB to 11.73 dB (p = 0.231). Conclusions: The addition of insulin in patients previously treated with the LRRT was associated with improved sensitivity and a stabilizing effect on neuroretinal function. Full article

Retinal detachment (RD) is a serious clinical condition that significantly impacts patients’ quality of life. Its management involves considering several clinical factors that may affect the therapeutic approach. Inflammatory complications can affect visual recovery, long-term outcomes, and prognosis. Understanding the underlying inflammatory mechanisms is key to improving personalized medicine and optimizing therapeutic approaches to management. This review comprehensively searched scientific databases (Medline, Web of Science, and Scopus), considering clinical and experimental studies published between 1999 and 2025. Specific MeSH terms and predefined inclusion and exclusion criteria were used to select the most relevant papers. A total of 140 studies were analyzed. The findings were analyzed qualitatively and illustrated with images from clinical practice. Several studies have demonstrated the critical role of cytokines in retinal inflammation, highlighting their importance in regulating the immune response following RD. In addition, oxidative stress, apoptotic mechanisms, and glia activation, particularly Müller cells and microglia, have been identified as crucial elements in the progression of retinal damage. In this sense, inflammation poses significant clinical challenges that require more effective therapeutic strategies. In conclusion, this review differs from previous literature by emphasizing the translational implications of inflammatory mechanisms in RD and by comparing experimental and clinical data. The management of RD should consider not only surgical aspects, but also modulation of the inflammatory response to improve visual outcomes and prevent long-term complications. Full article

O-mannosylation is a post-translational modification required for the proper function of various proteins and critical for development and growth. POMGNT1 encodes the enzyme O-linked-mannose β-1,2-N-acetylglucosaminyltransferase 1, which catalyzes the second step in the synthesis of α-dystroglycan O-mannosyl glycans. Among POMGNT1-related α-dystroglycanopathies, muscle–eye–brain (MEB) disease presents with congenital muscular dystrophy, structural brain abnormalities, and retinal dystrophy. Defects in protein O-mannosylation due to biallelic loss-of-function POMGNT1 mutations produce disturbances in assembling and organizing the basal membrane in the neuroretinal system, involving both the central and peripheral nervous systems. In the retina, POMGNT1 is expressed in photoreceptors and is localized near the photoreceptor cilium basal body, a structure critical for protein transport. Recent studies have reported an isolated degenerative ocular phenotype without any involvement of muscular or neuronal tissues. Here, we report on a family with three siblings affected by an apparently isolated clinically variable retinal disease and sharing biallelic inactivating POMGNT1 variants. Notably, the rod-cone dystrophy phenotype in the three siblings varied significantly in onset, presentation, and severity. These findings provide further evidence of the clinical variability associated with defective POMGNT1 function. Full article

Bartonella henselae is a Gram-negative bacillus, mainly parasitizing on cats. When a child is scratched by a cat, they may present with the disease symptoms including regional lymphadenopathy, malaise, fever, and splenomegaly, which is known as cat-scratch disease (CSD). Ocular manifestations occur in 5–10% of patients with CSD. Neuroretinitis is the most common, and, in addition, Parinaud oculoglandular syndrome, endophthalmitis, retinochoroiditis, vascular occlusions, multiple mass-like lesions resembling ocular metastases, serous macular detachments, and retinal vasoproliferative lesions may also occur. We report a case of unilateral exudative retinal detachment and uveitis with a large subretinal deposit on the macula in a 6-year-old female with CSD, along with lymphadenitis on her left thigh. To the best of our knowledge, this case of exudative retinal detachment and uveitis with a large subretinal deposit under the retina affecting the macular area above the optic disc has not been previously reported. Full article

Background/Objectives: Neuroretinitis (NR) is a rare inflammatory condition characterized by sudden vision loss, optic disc edema and macular star appearance predominantly affecting individuals in their third and fourth decades of life. Methods: This paper describes the case of 33-year-old Caucasian man with no significant medical history complaining of decreased vision for about a week. Results: The ophthalmological exam revealed best-corrected visual acuity (BCVA) for the right eye (RE) of 0.8 (decimal notation) and of 0.9 for the left eye (LE). Intraocular pressure (IOP) was 20 mmHg in RE and 18 mmHg in LE. Slit-lamp examination of both eyes (OU) showed no evidence of intraocular inflammation in the anterior chamber or vitreous cavity. Examination of the posterior pole of the right eye showed bilateral papilledema with an incomplete macular fan pattern. Conclusions: Despite extensive laboratory tests, including serologic and imaging investigations, a definitive etiology remained unclear. It is very important to differentiate NR from other optic nerve disorders, requiring careful clinical evaluation and observation of the evolution of symptoms. Full article

Recent advancements in clinical research have identified the need to combine pupillometry with a selective stimulation of the eye’s photoreceptor cell types to broaden retinal and neuroretinal health assessment opportunities. Our thorough analysis of the literature revealed the technological gaps that currently restrict and hinder the effective utilization of a method acknowledged to hold great potential. The available devices do not adequately stimulate the photoreceptor types with enough contrast and do not guarantee seamless device function integration, which would enable advanced data analysis. RetinaWISE is an advanced silencing pupillometry device that addresses these deficiencies. It combines a Maxwellian optical arrangement with advanced retinal stimulation, allowing for calibrated standard measurements to generate advanced and consistent results across multiple sites. The device holds a Class 1 CE marking under EU regulation 2017/745, thus facilitating clinical research progress. Full article

Cat-scratch disease (CSD) is an infectious disease caused by Bartonella henselae, presenting with fever and lymphadenopathy following contact with felines. The ocular manifestations include neuroretinitis, characterised by optic nerve swelling and a macular star. Case Presentation: We discuss a case of neuroretinitis that presented atypically, without a macular star. There was an initial suspicion of Bartonella, but the serology was negative. Our patient was eventually empirically treated for infective neuroretinitis based on a positive contact history (recently scratched by one of his three pet cats). There was progression to a macular star upon serial dilated fundus examination, and the repeated serology one week after symptom onset showed rising titres, supporting a diagnosis of CSD. Conclusions: A judicious review of systems, repeat assays, serial dilated fundus examination, and early ophthalmic evaluation are useful in cases of suspected neuroretinitis, remaining an important differential in the evaluation of sudden-onset painless vision loss and unilateral disc swelling. Full article

The proneural transcription factor atonal basic helix–loop–helix transcription factor 7 (ATOH7) is expressed in early progenitors in the developing neuroretina. In vertebrates, this is crucial for the development of retinal ganglion cells (RGCs), as mutant animals show an almost complete absence of RGCs, underdeveloped optic nerves, and aberrations in retinal vessel development. Human mutations are rare and result in autosomal recessive optic nerve hypoplasia (ONH) or severe vascular changes, diagnosed as autosomal recessive persistent hyperplasia of the primary vitreous (PHPVAR). To better understand the role of ATOH7 in neuroretinal development, we created ATOH7 knockout and eGFP-expressing ATOH7 reporter human induced pluripotent stem cells (hiPSCs), which were differentiated into early-stage retinal organoids. Target loci regulated by ATOH7 were identified by Cleavage Under Targets and Release Using Nuclease with sequencing (CUT&RUN-seq) and differential expression by RNA sequencing (RNA-seq) of wildtype and mutant organoid-derived reporter cells. Additionally, single-cell RNA sequencing (scRNA-seq) was performed on whole organoids to identify cell type-specific genes. Mutant organoids displayed substantial deficiency in axon sprouting, reduction in RGCs, and an increase in other cell types. We identified 469 differentially expressed target genes, with an overrepresentation of genes belonging to axon development/guidance and Notch signaling. Taken together, we consolidate the function of human ATOH7 in guiding progenitor competence by inducing RGC-specific genes while inhibiting other cell fates. Furthermore, we highlight candidate genes responsible for ATOH7-associated optic nerve and retinovascular anomalies, which sheds light to potential future therapy targets for related disorders. Full article

Glaucoma is a heterogeneous group of optic neuropathies characterized by a progressive degeneration of the retinal ganglion cells (RGCs), leading to irreversible vision loss. Nowadays, the traditional therapeutic approach to glaucoma consists of lowering the intraocular pressure (IOP), which does not address the neurodegenerative features of the disease. Besides animal models of glaucoma, there is a considerable need for in vitro experimental models to propose new therapeutic strategies for this ocular disease. In this study, we elucidated the pathological mechanisms leading to neuroretinal R28 cell death after exposure to glutamate and hydrogen peroxide (H₂O₂) in order to develop new therapeutic approaches for oxidative stress-induced retinal diseases, including glaucoma. We were able to show that glutamate and H₂O₂ can induce a decrease in R28 cell viability in a concentration-dependent manner. A cell viability of about 42% was found after exposure to 3 mM of glutamate and about 56% after exposure to 100 µM of H₂O₂ (n = 4). Label-free quantitative mass spectrometry analysis revealed differential alterations of 193 and 311 proteins in R28 cells exposed to 3 mM of glutamate and 100 µM of H₂O₂, respectively (FDR < 1%; p < 0.05). Bioinformatics analysis indicated that the protein changes were associated with the dysregulation of signaling pathways, which was similar to those observed in glaucoma. Thus, the proteomic alteration induced by glutamate was associated with the inhibition of the PI3K/AKT signaling pathway. On the other hand, H₂O₂-induced toxicity in R28 cells was linked to the activation of apoptosis signaling and the inhibition of the mTOR and ERK/MAPK signaling pathways. Furthermore, the data show a similarity in the inhibition of the EIF2 and AMPK signaling pathways and the activation of the sumoylation and WNT/β-catenin signaling pathways in both groups. Our findings suggest that the exposure of R28 cells to glutamate and H₂O₂ could induce glaucoma-like neurodegenerative features and potentially provide a suitable tool for the development of new therapeutic strategies for retinal diseases. Full article

Augmenting the natural melanocortin pathway in mouse eyes with uveitis or diabetes protects the retinas from degeneration. The retinal cells are protected from oxidative and apoptotic signals of death. Therefore, we investigated the effects of a therapeutic application of the melanocortin alpha-melanocyte-stimulating hormone (α-MSH) on an ischemia and reperfusion (I/R) model of retinal degenerative disease. Eyes were subjected to an I/R procedure and were treated with α-MSH. Retinal sections were histopathologically scored. Also, the retinal sections were immunostained for viable ganglion cells, activated Muller cells, microglial cells, and apoptosis. The I/R caused retinal deformation and ganglion cell loss that was significantly reduced in I/R eyes treated with α-MSH. While α-MSH treatment marginally reduced the number of GFAP-positive Muller cells, it significantly suppressed the density of Iba1-positive microglial cells in the I/R retinas. Within one hour after I/R, there was apoptosis in the ganglion cell layer, and by 48 h, there was apoptosis in all layers of the neuroretina. The α-MSH treatment significantly reduced and delayed the onset of apoptosis in the retinas of I/R eyes. The results demonstrate that therapeutically augmenting the melanocortin pathways preserves retinal structure and cell survival in eyes with progressive neuroretinal degenerative disease. Full article

This work aims to reveal the microscopic (2–3 micrometer resolution) appearance of human myelinated nerve fibers in vivo for the first time. We analyzed the myelinated retinal nerve fibers of a male patient without other neurological disorders in a non-invasive way using the transscleral optical phase imaging method with adaptive optics. We also analyzed the fellow eye with non-myelinated nerve fibers and compared the results with traditional ocular imaging methods such as optical coherence tomography. We documented the microscopic appearance of human myelin and myelinated axons in vivo. This method allowed us to obtain better details than through traditional ocular imaging methods. We hope these findings will be useful to the scientific community to evaluate neuro-retinal structures through new imaging techniques and more accurately document nerve anatomy and the pathophysiology of this disease. Full article

Multiple sclerosis (MS) and Alzheimer’s disease (AD) cause retinal thinning that is detectable in vivo using optical coherence tomography (OCT). To date, no papers have compared the two diseases in terms of the structural differences they produce in the retina. The purpose of this study is to analyse and compare the neuroretinal structure in MS patients, AD patients and healthy subjects using OCT. Spectral domain OCT was performed on 21 AD patients, 33 MS patients and 19 control subjects using the Posterior Pole protocol. The area under the receiver operating characteristic (AUROC) curve was used to analyse the differences between the cohorts in nine regions of the retinal nerve fibre layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL) and outer nuclear layer (ONL). The main differences between MS and AD are found in the ONL, in practically all the regions analysed (AUROC_FOVEAL = 0.80, AUROC_PARAFOVEAL = 0.85, AUROC_PERIFOVEAL = 0.80, AUROC__PMB = 0.77, AUROC_PARAMACULAR = 0.85, AUROC_{INFERO_NASAL} = 0.75, AUROC_{INFERO_TEMPORAL} = 0.83), and in the paramacular zone (AUROC_PARAMACULAR = 0.75) and infero-temporal quadrant (AUROC_{INFERO_TEMPORAL} = 0.80) of the GCL. In conclusion, our findings suggest that OCT data analysis could facilitate the differential diagnosis of MS and AD. Full article

Purpose: to assess the tomographic retinal layers’ thickness in eyes affected by branch retinal artery occlusion (BRAO) and to compare it to those of patients affected by primary open angle glaucoma (POAG). Methods: retrospective review of 27 patients; 16 with BRAO (16 eyes) and 11 with POAG (20 eyes) were identified among those who received SD-OCT scans, including analysis of macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), neuroretinal rim (NRR), circumpapillary RNFL at 3.5 mm and hemisphere asymmetry (HA). Results: the total IPL and INL thinning difference between the two groups was statistically significant (p = 0.0067 and p < 0.0001, respectively). The HA difference for the total macular thinning, mRNFL, GCL, IPL and INL (p < 0.0001) was also statistically significant. The analysis of the average total retinal thinning, total mRNFL and GCL thinning showed no statistically significant difference between the two groups. Conclusions: unilateral inner retinal thinning may represent a sign of temporal BRAO, particularly for INL thinning and HA difference over 17µm in total retinal layer thinning. This information is particularly useful in the diagnosis of previous, undiagnosed BRAO and may help prevent further retinal arterial occlusion and possible cerebrovascular incidents. Full article

Background and Objectives: Glaucoma is a major cause of irreversible visual impairment and blindness, so its timely detection is crucial. Retinal images from diabetic retinopathy screening programmes (DRSP) provide an opportunity to detect undiagnosed glaucoma. Our aim was to find out which retinal image indicators are most suitable for referring DRSP patients for glaucoma assessment and to determine the glaucoma detection potential of Slovenian DRSP. Materials and Methods: We reviewed retinal images of patients from the DRSP at the University Medical Centre Ljubljana (November 2019–January 2020, May–August 2020). Patients with at least one indicator and some randomly selected patients without indicators were invited for an eye examination. Suspect glaucoma and glaucoma patients were considered accurately referred. Logistic regression (LOGIT) with patients as statistical units and generalised estimating equation with logistic regression (GEE) with eyes as statistical units were used to determine the referral accuracy of indicators. Results: Of the 2230 patients reviewed, 209 patients (10.1%) had at least one indicator on a retinal image of either one eye or both eyes. A total of 149 (129 with at least one indicator and 20 without) attended the eye exam. Seventy-nine (53.0%) were glaucoma negative, 54 (36.2%) suspect glaucoma, and 16 (10.7%) glaucoma positive. Seven glaucoma patients were newly detected. Neuroretinal rim notch predicted glaucoma in all cases. The cup-to-disc ratio was the most important indicator for accurate referral (odds ratio 7.59 (95% CI 3.98–14.47; p < 0.001) and remained statistically significant multivariably. Family history of glaucoma also showed an impact (odds ratio 3.06 (95% CI 1.02–9.19; p = 0.046) but remained statistically significant only in the LOGIT multivariable model. Other indicators and confounders were not statistically significant in the multivariable models. Conclusions: Our results suggest that the neuroretinal rim notch and cup-to-disc ratio are the most important for accurate glaucoma referral from retinal images in DRSP. Approximately half of the glaucoma cases in DRSPs may be undiagnosed. Full article

Oxidative stress (OS) is involved in the pathogenesis of retinal neurodegenerative diseases such as age-related macular degeneration (AMD) and diabetic retinopathy (DR) and an important target of therapeutic treatments. New therapeutics are tested in vivo despite limits in terms of transferability and ethical concerns. Retina cultures using human tissue can deliver critical information and significantly reduce the number of animal experiments along with increased transferability. We cultured up to 32 retina samples derived from one eye, analyzed the model’s quality, induced OS, and tested the efficiency of antioxidative therapeutics. Bovine, porcine, rat, and human retinae were cultured in different experimental settings for 3–14 d. OS was induced by a high amount of glucose or hydrogen peroxide (H₂O₂) and treated with scutellarin, pigment epithelium-derived factor (PEDF), and/or granulocyte macrophage colony-stimulating factor (GM-CSF). The tissue morphology, cell viability, inflammation, and glutathione level were determined. The retina samples showed only moderate necrosis (23.83 ± 5.05 increased to 27.00 ± 1.66 AU PI-staining over 14 d) after 14 days in culture. OS was successfully induced (reduced ATP content of 288.3 ± 59.9 vs. 435.7 ± 166.8 nM ATP in the controls) and the antioxidants reduced OS-induced apoptosis (from 124.20 ± 51.09 to 60.80 ± 319.66 cells/image after the scutellarin treatment). Enhanced mammalian animal and human retina cultures enable reliable, highly transferable research on OS-triggered age-related diseases and pre-clinical testing during drug development. Full article