Purtscher\'s retinopathy is an occlusive micro-vasculopathy causing sudden onset visual loss in trauma. Similar retinal appearance is observed as a rare complication of acute pancreatitis which is identified as Purtscher-like retinopathy (PulR). We report the case of a 15-year-old girl diagnosed to have acute on chronic pancreatitis who noticed a sudden onset loss of vision in the left eye and was found to have significantly diminished visual acuity. A dilated fundoscopic examination demonstrated pathognomonic Purtscher flecken, multiple retinal haemorrhages, cotton wool spots and macular oedema. A clinical diagnosis of PulR was made in the setting of acute on chronic pancreatitis. Optical coherence tomography was used to support the diagnosis and to monitor response to therapy. Given the variable prognosis with no evidence-based therapies available, she had a subjective improvement in visual acuity with administration of intravitreal steroids and observation with management of the acute episode of pancreatitis. Knowledge and awareness of this rare condition will enable its early detection and the search for newer therapies.

OBJECTIVE: This review presents specific insights on the molecular underpinnings of the connection between fluorosis, type 2 diabetes, and microvascular complications, along with the novel biomarkers that are available for early detection.
CONCLUSIONS: Fluoride is an essential trace element for the mineralization of teeth and bones in humans. Exposure to higher concentrations of fluoride has harmful effects that significantly outweigh its advantageous ones. Dental fluorosis and skeletal fluorosis are the common side effects of exposure to fluoride, which affect millions of individuals globally. Alongside, it also causes non-skeletal fluorosis, which affects the population suffering from non-communicable diseases like diabetes by impacting the soft tissues and causing diabetic microvascular complications. Previous studies reported the prevalence range of these diabetic complications of neuropathy (3-65 %), nephropathy (1-63 %), and retinopathy (2-33 %). Fluoride contributes to the development of these complications by causing oxidative stress, cellular damage, degrading the functioning capability of mitochondria, and thickening the retinal vein basement.
CONCLUSIONS: Early diagnosis is a prompt way of prevention, and for that, biomarkers have emerged as an innovative and useful technique. This allows healthcare practitioners and policymakers in endemic areas to comprehend the molecular complexities involved in the advancement of diabetic microvascular problems in the context of high fluoride exposure.

One vision-threatening side effect of systematic diabetes mellitus is diabetic retinopathy (DR). Recent studies have revealed that the development and progression of DR depend critically on inflammation resulting from diabetes. By attracting leukocytes to endothelium, the higher production of the inflammatory mediators induces degeneration of retinal capillaries, hence increasing vascular permeability and thrombosis probability. The leukocytes that are recruited eventually generate additional proinflammatory and proangiogenic substances, resulting in the increased infiltration of leukocytes in the retina. This process also leads to changes in the blood retinal barrier and the formation of new blood vessels, which helps to counteract the damage caused by the blockage of blood flow. IL-12 family members, IL-12, IL-23, IL-27, and IL-35, play a crucial role in regulating the responses of T helper (Th)1 and Th17 cell populations. The collected data from studies investigating the levels of IL-12 family members in the blood and eye tissues suggest that IL-12 is linked to DR, indicating that it may have a role in the development of DR as a sequential component of the immune response. This review specifically examines the possibility of using IL-12 family cytokines as a therapeutic approach for diabetes, taking into consideration their involvement in the development of DR.

Malattia Leventinese/Doyne honeycomb retinal dystrophy (ML/DHRD) is an age-related macular degeneration-like (AMD-like) retinal dystrophy caused by an autosomal dominant R345W mutation in the secreted glycoprotein, fibulin-3 (F3). To identify new small molecules that reduce F3 production in retinal pigmented epithelium (RPE) cells, we knocked-in a luminescent peptide tag (HiBiT) into the endogenous F3 locus that enabled simple, sensitive, and high-throughput detection of the protein. The GSK3 inhibitor, CHIR99021 (CHIR), significantly reduced F3 burden (expression, secretion, and intracellular levels) in immortalized RPE and non-RPE cells. Low-level, long-term CHIR treatment promoted remodeling of the RPE extracellular matrix, reducing sub-RPE deposit-associated proteins (e.g., amelotin, complement component 3, collagen IV, and fibronectin), while increasing RPE differentiation factors (e.g., tyrosinase, and pigment epithelium-derived factor). In vivo, treatment of 8-month-old R345W+/+ knockin mice with CHIR (25 mg/kg i.p., 1 mo) was well tolerated and significantly reduced R345W F3-associated AMD-like basal laminar deposit number and size, thereby preventing the main pathological feature in these mice. This is an important demonstration of small molecule-based prevention of AMD-like pathology in ML/DHRD mice and may herald a rejuvenation of interest in GSK3 inhibition for the treatment of retinal degenerative diseases, including potentially AMD itself.

Human embryonic stem cells and human induced pluripotent stem cells may be used to create 3D tissues called brain organoids. They duplicate the physiological and pathological characteristics of human brain tissue more faithfully in terms of both structure and function, and they more precisely resemble the morphology and cellular structure of the human embryonic brain. This makes them valuable models for both drug screening and in vitro studies on the development of the human brain and associated disorders. The technical breakthroughs enabled by brain organoids have a significant impact on the research of different brain regions, brain development and sickness, the connections between the brain and other tissues and organs, and brain evolution. This article discusses the development of brain organoids, their use in diabetes research, and their progress.

BACKGROUND: An increasing amount of people are globally affected by retinal diseases, such as diabetes, vascular occlusions, maculopathy, alterations of systemic circulation, and metabolic syndrome.
OBJECTIVE: This review will discuss novel technologies in and potential approaches to the detection and diagnosis of retinal diseases with the support of cutting-edge machines and artificial intelligence (AI).
METHODS: The demand for retinal diagnostic imaging exams has increased, but the number of eye physicians or technicians is too little to meet the request. Thus, algorithms based on AI have been used, representing valid support for early detection and helping doctors to give diagnoses and make differential diagnosis. AI helps patients living far from hub centers to have tests and quick initial diagnosis, allowing them not to waste time in movements and waiting time for medical reply.
RESULTS: Highly automated systems for screening, early diagnosis, grading and tailored therapy will facilitate the care of people, even in remote lands or countries.
CONCLUSIONS: A potential massive and extensive use of AI might optimize the automated detection of tiny retinal alterations, allowing eye doctors to perform their best clinical assistance and to set the best options for the treatment of retinal diseases.

Diabetes is prevalent worldwide, with >90% of the cases identified as Type 2 diabetes. High blood sugar (hyperglycemia) is the hallmark symptom of diabetes, with prolonged and uncontrolled levels contributing to subsequent complications. Animal models have been used to study these complications, which include retinopathy, nephropathy, and peripheral neuropathy. More recent studies have focused on cognitive behaviors due to the increased risk of dementia/cognitive deficits that are reported to occur in older Type 2 diabetic patients. In this review, we collate the data reported from specific animal models (i.e., mouse, rat, zebrafish) that have been examined for changes in both retina/vision (retinopathy) and brain/cognition, including db/db mice, Goto-Kakizaki rats, Zucker Diabetic Fatty rats, high-fat diet-fed rodents and zebrafish, and hyperglycemic zebrafish induced by glucose immersion. These models were selected because rodents are widely recognized as established models for studying diabetic complications, while zebrafish represent a newer model in this field. Our goal is to (1) summarize the published findings relevant to these models, (2) identify similarities in cellular mechanisms underlying the disease progression that occur in both tissues, and (3) address the hypothesis that hyperglycemic-induced changes in retina precede or predict later complications in brain.

BACKGROUND: Prior case reports and animal studies have reported on potential ophthalmologic complications of babesiosis, but this issue has not previously been addressed in a cohort of patients with babesiosis. This cross-sectional descriptive pilot study evaluated the retinas of patients with acute babesiosis to determine if retinal abnormalities are a feature of the disease.
METHODS: We screened all patients admitted to Yale New Haven Hospital with laboratory confirmed babesiosis during the summer of 2023 and obtained informed consent. Patients were interviewed and underwent pupil dilation and a retinal examination using an indirect ophthalmoscope. Demographic and clinical information were obtained by questionnaire and through chart review.
RESULTS: Ten patients underwent retinal eye exams with results that were generally unremarkable. No study patients showed any signs of retinal inflammation, infection, retinal bleeding, retinal tears, or abnormal vessel formation that could be attributed to infection.
CONCLUSIONS: This small study did not find evidence of retinopathy in patients with babesiosis. Further studies with larger populations, repeated exams, and long term follow up will further elucidate the potential small vessel complications of human babesiosis.

Neovascular age-related macular degeneration (nAMD) remains a major cause of visual impairment and puts considerable burden on patients and health care systems. L-DOPA-treated Parkinson Disease (PD) patients have been shown to be partially protected from nAMD, but the mechanism remains unknown. Using murine models, combining 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD and laser-induced nAMD, standard PD treatment of L-DOPA/DOPA-decarboxylase inhibitor, or specific dopamine receptor inhibitors, we here demonstrate that L-DOPA treatment-induced increase of dopamine mediated dopamine receptor D2 (DRD2) signaling inhibits choroidal neovascularization independently of MPTP-associated nigrostriatal pathway lesion. Analyzing a retrospective cohort of more than two hundred thousand nAMD patients receiving anti-VEGF treatment from the French nationwide insurance database, we show that DRD2-agonist treated (PD) patients have a significantly delayed age of onset for nAMD (81.4 (±7.0) vs 79.4 (±8.1) years old, respectively, p<0.0001) and reduced need for anti-VEGF therapies (-0.6 injections per 100 mg/day daily dose of DRD2 agonists the second year of treatment), similar to the L-DOPA treatment. While providing a mechanistic explanation for an intriguing epidemiological observation, our findings suggest that systemic DRD2 agonists might constitute an adjuvant therapy to delay and reduce the need for anti-VEGF therapy in nAMD patients.

Angiogenesis is a highly coordinated process involving the control of various endothelial cell behaviors. Mechanisms for transcription factor involvement in the regulation of endothelial cell dynamics and angiogenesis have become better understood, however much remains unknown, especially the role of non-DNA binding transcriptional cofactors. Here, we show that Zmiz1, a transcription cofactor, is enriched in the endothelium and critical for embryonic vascular development, postnatal retinal angiogenesis, and pathological angiogenesis in oxygen induced retinopathy (OIR). In mice, endothelial cell-specific deletion of Zmiz1 during embryogenesis led to lethality due to abnormal angiogenesis and vascular defects. Inducible endothelial cell-specific ablation of Zmiz1 postnatally resulted in impaired retinal vascular outgrowth, decreased vascular density, and increased vessel regression. In addition, angiogenic sprouting in the superficial and deep layers of the retina was markedly reduced. Correspondingly, vascular sprouting in fibrin bead assays was significantly reduced in the absence of Zmiz1, while further in vitro and in vivo evidence also suggested deficits in EC migration. In agreement with the defective sprouting angiogenesis phenotype, gene expression analysis of isolated retinal endothelial cells revealed downregulation of tip-cell enriched genes upon inactivation of Zmiz1. Lastly, our study suggested that endothelial Zmiz1 is critical for intraretinal revascularization following hypoxia exposure in the OIR model. Taken together, these findings begin to define the previously unspecified role of endothelial Zmiz1 in physiological and pathological angiogenesis.