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Alzheimer’s disease (AD) is marked by cognitive decline, and also by retinal degeneration. Having in mind that docosahexaenoic acid (DHA, 22:6n − 3) is a safe, low-cost, and pivotal fatty acid for brain health and sustained cognitive function, this study exploits environmentally friendly non-fish sources as potential dietary supplements enriched with DHA to prevent or reverse AD. Forty 5xFAD transgenic male mice, aged five weeks old, were randomly distributed by five body weight-matched dietary groups (with eight animals each) and fed isocaloric diets based on the AIN-93M standard formulation for rodents for 6 months. Except for the control feed (without supplementation), each diet contained a modified lipidic fraction supplemented with 2% of the following: (1) linseed oil (LSO, rich in alpha-linolenic acid (ALA, 18:3n − 3)); (2) cod liver oil (fish oil, FO, rich in both DHA and eicosapentaenoic acid (EPA, 20:5n − 3)); (3) Schizochytrium sp. microalga oil (Schizo, with 40% of DHA); and (4) commercial DHASCO (DHASCO, with 70% of DHA). The aim of this study was to measure retinal neural layer thickness, calculate ganglion cell layer (GCL) density, and assess retinal injury by means of immunohistochemical staining for β-amyloid plaques deposition, TAU protein levels, and IBA1, as hallmark features of AD progression, in order to elucidate the effects of different dietary DHA treatments in Alzheimer’s retinas. Although no statistical differences were observed across retinal layer thicknesses depending on the diet (p > 0.05), there was a consistent pattern for slightly increased retinal thickness in 5xFAD mice fed fish oil relative to the others for the measurement of total layers, in general and for the inner segment/outer segment layer, the outer nuclear layer, the outer plexiform layer, the inner nuclear layer, and the inner plexiform layer, in particular. The ganglion cell layer (GCL) density was increased in 5xFAD mice fed the DHASCO oil diet relative to the control (p < 0.05), suggesting a benefit of DHA supplementation on the number of viable ganglion cells. No positive staining was observed for β-amyloid plaques deposition or the neuroinflammatory marker, IBA1, corroborating previous findings in human AD retinas. Conversely, the internal retinal layers showed intense TAU immunostaining. Immnunostained TAU area was significantly reduced in 5xFAD mice fed a fish oil diet compared to control (p < 0.05), although the number of TAU-positive cells did not differ across diets (p > 0.05). The retinal protected integrity derived from the benefits of DHA supplementation found, either from fish oil or DHASCO oil, underscores the potential of retinal biomarkers as non-invasive indicators of cognitive decline and overall brain health, opening new avenues for investigating AD pathophysiology in the retina.

This study aimed to investigate the metabolic alterations in the vitreous humor of patients with diabetes across different stages of diabetic retinopathy (DR) and explore potential dietary interventions to mitigate these changes. Vitreous samples were collected from 23 patients undergoing vitrectomy and grouped into controls, diabetic without DR, non-proliferative DR (NPDR), and proliferative DR (PDR). Metabolomic analysis was performed using mass spectrometry, focusing on identifying significantly altered metabolites. A total of 82 features were identified, of which several were significantly reduced in DR compared to controls. Ascorbate and taurine were notably lower in NPDR ( < 0.01), while choline and N-acetylaspartic acid were significantly reduced in NPDR and PDR ( < 0.01). Tagatose was significantly reduced in PDR ( < 0.05), while stachydrine and serine displayed biphasic trends, decreasing in NPDR ( < 0.001; < 0.05) but increasing in PDR ( < 0.05). The results suggest that key metabolites involved in antioxidant defense, membrane integrity, and neuronal function are disrupted in the vitreous humor of patients with DR. Dietary supplementation targeting these metabolic deficiencies, such as increased intake of ascorbate, taurine, serine, choline, and stachydrine, may offer adjunctive support in managing DR progression.

Retinal degeneration is a progressive condition that affects the retina, the light-sensitive layer, and deteriorates the inner retinal cells that encompass retinal pigment epithelium, photoreceptors, and ganglion cells that are essential for eyesight. Multiple factors including aging, genetic factors, oxidative stress, inflammation, and environmental factors can contribute to retinal degeneration. Retinal degeneration is seen predominantly in Age-related Macular degeneration, Diabetic retinopathy, Glaucoma, and Retinitis pigmentosa that contribute to the leading cause of vision loss. The search for potential and effective therapeutic interventions in the management of retinal degeneration has led to increased interest in dietary supplements, particularly those rich in antioxidant properties. Dietary supplements have been proposed as an ideal source for preventing retinal degeneration, especially supplements containing significant levels of antioxidants that help to reduce the damage to retinal cells. Notably, dietary interventions with carotenoids, flavonoids, alkaloids, amino acids, fatty acids, vitamins, and minerals have shown positive effects in both preclinical and clinical studies by preserving the retinal structure, revitalizing retinal health, delaying disease progression, and improving visual function. To explore this topic further, a systematic search strategy was employed in recent studies that are focused on cell lines, animal models, and human subjects. Ultimately, this review highlights the potential of dietary supplements that should be used as adjunctive therapies alongside comprehensive medical management, aiming to maximize their potential benefits in treating and preventing retinal degeneration.

Abstract Background/Objectives: To investigate in adolescents the relationships between retinal vessel diameter, physical fitness, insulin sensitivity, and systemic inflammation. Methods: We evaluated 157 adolescents, 112 with excessive weight and 45 lean, all without type 2 diabetes mellitus. All received detailed evaluations, including measurements of retinal vessel diameter, insulin sensitivity, levels of inflammation, and physical fitness. Results: Overweight/obese adolescents had significantly narrower retinal arteriolar and wider venular diameters, significantly lower insulin sensitivity, and physical fitness. They also had decreased levels of anti-inflammatory and increased levels of proinflammatory markers as well as an overall higher inflammation balance score. Fitness was associated with larger retinal arteriolar and narrower venular diameters and these relationships were mediated by insulin sensitivity. We demonstrate that inflammation also mediates the relationship between fitness and retinal venular, but not arterial diameter; insulin sensitivity and inflammation balance score jointly mediate this relationship with little overlap in their effects. Conclusions: Increasing fitness and insulin sensitivity and reducing inflammation among adolescents carrying excess weight may improve microvascular integrity. Interventions to improve physical fitness and insulin function and reduce inflammation in adolescents, a group likely to benefit from such interventions, may reduce not only cardiovascular disease in middle age, but also improve cerebrovascular function later in life.

The retinal microvasculature is a window to the systemic circulation. Systemic diseases, like diabetes and hypertension, are linked to retinal microvascular structure changes (as width, tortuosity, and branching angle). The latter results in a potentially disadvantageous blood flow. This study has been designed to examine the relationship of a retinal vascular tortuosity to both blood pressure and velocity. The geometrical outlines of realistic retinal vascular trees have been extracted from fundus images. The retinal venular tortuosity has been quantitatively measured. A normal tortuosity value has been found, which has not exceeded 1.2. A computational fluid dynamics study has been conducted to examine the effect of topological changes on the hemodynamics distribution in the retinal circulation. The microvascular diameter effect (i.e., Fahraeus–Lindqvist effect) and the hematocrit have been considered in determining the viscosity of the blood in the retinal vessel segments. The pressure drop and the maximum velocity have been in the order of 15 mmHg and 0.032 m/s for tortuous vessels, and 13 mmHg and 0.054 m/s for normal vessels, respectively. For a clinical case, the maximal velocity falls down to 14 % due to the tortuosity. The current results have shown a decrease in the blood velocity and an increase in the pressure drop with tortuosity, which are in good agreement with in vivo measurements reported in the literature.

Degeneration of the retinal pigmented epithelium (RPE) and aberrant blood vessel growth in the eye are advanced-stage processes in blinding diseases such as age-related macular degeneration (AMD), which affect hundreds of millions of people worldwide. Loss of the RNase DICER1, an essential factor in micro-RNA biogenesis, is implicated in RPE atrophy. However, the functional implications of DICER1 loss in choroidal and retinal neovascularization are unknown. Here, we report that two independent hypomorphic mouse strains, as well as a separate model of postnatal RPE-specific DICER1 ablation, all presented with spontaneous RPE degeneration and choroidal and retinal neovascularization. DICER1 hypomorphic mice lacking critical inflammasome components or the innate immune adaptor MyD88 developed less severe RPE atrophy and pathological neovascularization. DICER1 abundance was also reduced in retinas of the JR5558 mouse model of spontaneous choroidal neovascularization. Finally, adenoassociated vector-mediated gene delivery of a truncated DICER1 variant (OptiDicer) reduced spontaneous choroidal neovascularization in JR5558 mice. Collectively, these findings significantly expand the repertoire of DICER1 in preserving retinal homeostasis by preventing both RPE degeneration and pathological neovascularization.

PurposeTo test if an encircling band improves outcomes in vitrectomy for pseudophakic retinal detachment (PRD) with inferior or with multiple (4 or more) breaks.MethodsSubgroup analysis of a prospective randomized controlled multicenter trial in patients with uncomplicated PRD assigned either to 20 G vitrectomy plus encircling band (group E1), or 20 G vitrectomy without any buckle (group C), or 23/25 G vitrectomy without any buckle (group E2). The primary endpoint was defined as no indication for any retina reattaching procedure during the review period of 6 months. One hundred out of 257 patients were identified with inferior breaks and 63 patients had 4 or more breaks.ResultsIn patients with retinal breaks between 5:00 and 7:00, treatment was successful in 77.4% (24/31, treatment arm E1) versus 57.1% (16/28, treatment arm C) (p = 0.301, odds ratio (OR) 1.83, 95% confidence interval (CI) 0.48 to 7.17). In patients with multiple breaks, success rates were 68.2% (15/22, E1) versus. 72.4% (21/29, C, p = 0.46, OR 0.52, CI 0.08–3.65).ConclusionCombining an encircling band with vitrectomy in patients with pseudophakic retinal detachment and inferior or multiple breaks does not significantly improve primary anatomical success in comparison to treatment with 20 G or 23/25 G vitrectomy alone.

Purpose To compare the rate of re-detachment in patients with rhegmatogenous retinal detachment and Grade-C PVR following vitreoretinal surgery, with and without serial intravitreal injections of methotrexate. Methods It was a randomized control trial. Patients aged more than 18 years undergoing pars plana vitrectomy for rhegmatogenous retinal detachment with PVR grade C or more were included in the study. Patients treated with intravitreal injection of methotrexate were grouped as cases and those not injected served as controls. The cases received 3 intravitreal injections of methotrexate at monthly intervals. Patients were evaluated on Day 1, 1st month, 2nd month, 3rd month and 6th month in terms of BCVA, rate of re-attachment and grade of PVR. Results The case group had 23 patients and the control group had 20 patients. 2 patients in the case group were lost to follow-up after the first follow-up, so they were excluded. So 21 patients in case group and 20 patients in control group were followed up. Six months after surgery, 15 ‘cases’ had completely attached retina whereas 6 patients had partial detachment with macula on. There was no patient amongst the cases with macula-off retinal re-detachment. Out of 20 patients in the control group, 9 had a complete retinal attachment, 4 had partial detachment with macula-on and 7 had partial detachment with macula-off. There was statistically significant difference in macula off retinal detachment rates ( p -value- 0.003). Conclusion Serial intravitreal methotrexate injections reduce the incidence of re-detachment in patients undergoing PPV for RRD with PVR-C. Further investigation into this promising therapeutic approach is warranted. Key messages What is known Methotrexate is an anti-inflammatory agent which is safe for intravitreal use There are case series retrospective and prospective studies suggesting potential benefit of intravitreal methotrexate in preventing re-detachment due to PVR What is new First randomized control trial studying the efficacy of intravitreal methotrexate in preventing re-detachment due to PVR Our study showed statistically significant difference in macula off retinal detachment between the 2 groups at 6 months of follow up

Background Neovascular glaucoma (NVG) is rare, comprising only 3.9% of all glaucoma cases. The most common cause of NVG is ischaemic central retinal vein occlusion (iCRVO). NVG frequently results in blindness and painful end-stage glaucomatous damage leading to the need for enucleation. Currently, there is no preventive therapy for NVG following iCRVO. Rescue treatments have severe drawbacks. Accordingly, there is a great need for preventing the often visually devastating outcomes of NVG. The STRONG study is designed to test whether the topically active anti-angiogenic agent aganirsen is able to inhibit the formation of neovascularisation leading to the development of secondary NVG in eyes with iCRVO. At the same time, STRONG will provide important information on the natural course of iCRVO and NVG in a large and well-characterised cohort of such patients. Methods/design This protocol describes a phase II/III, prospective, randomised, placebo-controlled, double-masked, three-armed multicentre study for the investigation of aganirsen, a new topical treatment for iCRVO in order to prevent NVG. The study will evaluate the efficacy of two different doses of this newly developed antisense oligonucleotide formulated in an eye emulsion to avoid new vessel formation by blocking insulin receptor substrate-1 (IRS)-1. This leads to subsequent down-regulation of both angiogenic as well as proinflammatory growth factors such as vascular endothelial growth factor (VEGF) and tumour necrosis factor (TNF). Eligible patients ( n  = 333) will be treated with topical aganirsen or placebo for a period of 24 weeks. They will also be invited to participate in substudies involving analysis of gonioscopic images, detection of biomarkers for NVG and risk factors for iCRVO. Discussion The STRONG study has the potential to offer a new treatment modality for patients suffering from iCRVO with a high risk of developing NVG. The topical administration can reduce patients’ burden and risk related to rescue treatment, such as destructive laser treatment or enucleation, but requires a high level of patient compliance. Trial registration EudraCT: 2014-000239-18; ClinicalTrials.gov, ID: NCT02947867 . (Registered on 15 October 2016); see also http://strong-nvg.com .

Background Central retinal artery occlusion (CRAO) causes irreversible vision loss through ischemia-reperfusion (I/R) injury, characterized by oxidative stress and retinal ganglion cell (RGC) death. Current therapies are inadequate. This study investigates kynurenine (Kyn)—a tryptophan metabolite—as a novel therapeutic agent targeting dual pathways to combat retinal I/R injury. Methods The unilateral pterygopalatine ophthalmic artery occlusion (UPOAO) model was established by inserting a silicone filament embolus into the pterygopalatine artery. The detection of tryptophan metabolites in serum and retinal tissues was carried out using metabolomics. In the UPOAO mouse model, kynurenine (Kyn) was administered via intravitreal injection. Simultaneously, R28 retinal cells were treated with Kyn during oxygen-glucose deprivation (OGD) induction to model ischemic injury in vitro. Electroretinography (ERG) was performed to examine the visual function of the mice. Western blot analysis and immunofluorescence were used to detect the apoptosis level of retinal ganglion cells (RGCs). The role of Kyn in activating the aryl hydrocarbon receptor (AhR) to reduce oxidative stress in RGCs was demonstrated by using an AhR inhibitor. Results The neuroprotective effects of Kyn are mediated by a dual pathway: activation of the AhR-Nrf2 signaling axis, which transcriptionally upregulates antioxidant genes to mitigate oxidative stress, and modulation of downstream kynurenine pathway (KP) metabolites. While AhR-Nrf2 signaling provides transcriptional support for redox homeostasis, KP metabolites directly scavenge reactive oxygen species, synergistically counteracting oxidative damage and energy deficits in RIR injury. Conclusions Our findings highlight Kyn as a pathway-specific therapeutic candidate for CRAO, with potential for receptor-targeted and metabolic modulation strategies in treating retinal ischemia-reperfusion injuries.