Idiopathic Epiretinal Membrane: Microvasculature Analysis with Optical Coherence Tomography and Optical Coherence Tomography Angiography

Background: The present study examined the relationships among macular microvasculature, retinal structure, and epiretinal membrane (ERM) and explored the utility of optical coherence tomography (OCT) angiography (OCTA) in idiopathic ERM assessment. Methods: The study sample comprised 276 eyes of 276 patients. A total of 154 eyes with ERM and 122 normal (control) eyes were analyzed. Only one eye of each participant was randomly selected for posterior segment imaging. Each patient underwent OCT and OCTA. Images were analyzed with AngioTool 0.6. Results: Foveal avascular zone was significantly smaller in the ERM group (p = 0.044). Average retinal thickness and foveal thickness were significantly higher in the ERM group (both p = 0.001). Moreover, 64 (41.5%) patients exhibited no metamorphopsia, while 46 (29.8%) and 44 (28.7%) patients exhibited moderate and extensive metamorphopsias, respectively. Meanwhile, FAZ was negatively correlated with central retinal thickness in the ERM group. The vessel area (p = 0.0017) and vessel percentage area (p = 0.044) were significantly greater in the ERM group. Conclusions: Changes observed in the superficial plexus in OCTA are related to the severity of metamorphopsia and can be further evaluated to support decision making regarding the surgical management of idiopathic ERM.

Altered retinal structure and function in Spinocerebellar ataxia type 3

Spinocerebellar ataxia type 3 is an autosomal dominant neurodegenerative disorder caused by expansion of a polyglutamine (polyQ)-encoding CAG repeat in the ATXN3 gene. Because the ATXN3 protein regulates photoreceptor ciliogenesis and phagocytosis, we aimed to explore whether expanded polyQ ATXN3 impacts retinal function and integrity in SCA3 patients and transgenic mice. We evaluated the retinal structure and function in five patients with Spinocerebellar ataxia type 3 and in a transgenic mouse model of this disease (YACMJD84.2, Q84) using, respectively, optical coherence tomography (OCT) and electroretinogram (ERG). We further determined in the transgenic mice: a) the retinal expression pattern of ATXN3 and assessed the distribution of cones and rods by immunofluorescence (IF); and b) the retinal ultrastructure by transmission electron microscopy (TEM). Some patients with Spinocerebellar ataxia type 3 in our cohort revealed: i) reduced central macular thickness indirectly correlated with disease duration; ii) decreased thickness of the macula and the ganglion cell layer, and reduced macula volume inversely correlated with disease severity (SARA score); and iii) electrophysiological dysfunction of cones, rods, and inner retinal cells. Transgenic mice replicated the human OCT and ERG findings with aged homozygous Q84/Q84 mice showing a stronger phenotype accompanied by further thinning of the outer nuclear layer and photoreceptor layer and highly reduced cone and rod activities, thus supporting severe retinal dysfunction in these mice. In addition, Q84 mice showed progressive accumulation of ATXN3-positive aggregates throughout several retinal layers and depletion of cones alongside the disease course. TEM analysis of aged Q84/Q84 mouse retinas supported the IF ATXN3 aggregation findings by revealing the presence of high number of negative electron dense puncta in ganglion cells, inner plexiform and inner nuclear layers, and further showed thinning of the outer plexiform layer, thickening of the retinal pigment epithelium and elongation of apical microvilli. Our results indicate that retinal alterations detected by non-invasive eye examination using OCT and ERG could represent a biological marker of disease progression and severity in patients with Spinocerebellar ataxia type 3.

Protective effects of umbilical cord mesenchymal stem cell exosomes in a diabetic rat model through live retinal imaging

AIM: To assess the protective effect of human umbilical cord mesenchymal stem cell exosomes (hucMSC-Exs) in a diabetic rat model by using a variety of retinal bioassays. METHODS: hucMSCs were subjected to differential ultracentrifugation for the collection of exosomes, and transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) using a NanoSight analysis system and Western blotting (WB) were used to analyze the expression of surface marker proteins such as CD63, CD9 and Calnexin. Streptozotocin (STZ) was injected into the intraperitoneal cavity to establish a diabetic model. Rats were divided into a normal group, diabetic group and hucMSC-Ex group. Fundus fluorescein angiography (FFA), optical coherence tomography (OCT) and other live imaging methods were used to observe the fundus of the rats. Finally, the eyeballs of rats from each group were collected for hematoxylin-eosin (HE) staining to further analyze the retinal structure. RESULTS: Through TEM, NTA and WB, we successfully isolated hucMSC-Exs. Subsequent FFA and OCT confirmed that hucMSC-Exs effectively prevented early retinal vascular damage and thickening of the retina. Finally, HE staining of rat retinal sections revealed that exosomes effectively alleviated retinal structure disruption caused by diabetes. CONCLUSION: hucMSC-Exs have a protective effect on the retina in diabetic rat through FFA, OCT and HE staining.

A comparison of the retinal structure in the zebra-snout seahorse (Hippocampus barbouri Jordan & Richardson, 1908) between juveniles and adults in captivity

The activity of the sensory organ in the eye structure of the teleost fish is essential as it plays an important role in regulating fish-feeding behaviours. Unfortunately, the above information of zebra-snout seahorse Hippocampus barbouri, an aquaculture species in Thailand, has not been described. In this study, the eye structure, together with the retinal structure of juvenile [5th and 20th day after birth (DAB)] and adult (35th DAB), H. barbouri reared in captivity was investigated. All DABs were carried out and histologically observed. Light microscopic level explored the external-lateral surface of eye structure of H. barbouri, which consisted of the external, middle, and inner layers, as similarly reported in other teleost species. A well-differentiated retinal and photoreceptor cell layer were observed at 35th DAB compared to that at other DABs. This feature might be adequate to support the base of the increased feeding activity of adult seahorse in captivity for further research.

Construction of Hyaluronic Acid-CeO2 Conjugated Composite Nanoparticles and Their Activity Efficiency in Diabetic Retinopathy Alleviation

We developed an effective nanoparticle-biomaterial in alleviating diabetic retinopathy (DR), hyaluronic acid (HA)-CeO2, composed mainly of CeO2 and HA. To demonstrate its anti-DR capacity, retinal cells from a B6/J mouse model were used to compare the efficiency of PEI-CeO2 and HA-CeO2. We investigated the transport performance, histolysis, immune cell infiltration, angiogenesis, and hyperemia induced by the transport system. The structural integrity, microvascular apoptosis, and superoxide and peroxide concentrations in the retina were measured to evaluate the clinical efficacy of CeO2. The infiltration efficiency of HA-CeO2 was higher than that of PEI-CeO2. Lower levels of foreign body reaction were evident for HA-CeO2 with less histolysis, immune cell infiltration, angiogenesis, and hyperemia. The clinical efficacy of HA-CeO2 in terms of preservation of retinal structure and lowering of microvascular apoptosis and superoxide and peroxide concentrations was superior to those of PEI-CP. HA-CeO2 was shown to have significant antioxidation and anti-vascular injury capacity in a mouse model, and may be a potential compound nanodrug for DR treatment in the future.

Retinal Neuropathy in IGT Stage of OLETF Rats: Another Characteristic Change of Diabetic Retinopathy

Aims. We investigated the changes of retinal structure in normal glucose tolerance (NGT), impaired glucose tolerance (IGT), diabetes mellitus (DM), and diabetic kidney disease (DKD) stages in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Methods. We assigned OLETF rats to four groups based on their OGTT results and 24 h urinary microalbumin (24 h UMA) levels: NGT, IGT, DM, and DKD groups. We observed the structural and the corresponding pathological changes and quantified the expression of HIF-1α, iNOS, NF-κB, VEGF, ICAM-1, and occludin in the retina. Results. Significant damage to the retinal structure, especially in retinal ganglion cells (RGCs), was observed in the IGT stage. The expression of HIF-1α, iNOS, NF-κB, VEGF, and ICAM-1 was significantly upregulated, while that of occludin was downregulated. Conclusion. Significant retinal neuropathy occurs in the IGT stage. Inflammation and hypoxia may damage the blood retina barrier (BRB), leading to diabetic retinopathy.

Protective effect of LIF-huMSCs on the retina of diabetic model rats

AIM: To investigate the protective effect of human umbilical cord mesenchymal stem cells (hUCMSCs) modified by the LIF gene on the retinal function of diabetic model rats and preliminarily explore the possible mechanism. METHODS: A stably transfected cell line of hUCMSCs overexpressing leukemia inhibitory factor (LIF) was constructed. Overexpression was verified by fluorescent quantitative polymerase chain reaction (qPCR). Forty-eight adult Sprague-Dawley rats were randomly divided into a normal control group (group A), streptozotocin-induced diabetic control group (group B), diabetic rats at 3mo injected with empty vector-transfected hUCMSCs (group C) or injected with LIF-hUCMSCs (group D). Four weeks after the intravitreal injection, analyses in all groups included retinal function using flash electroretinogram (F-ERG), retinal blood vessel examination of retinal flat mounts perfused with fluorescein isothiocyanate-dextran (FITC-dextran), and retinal structure examination of sections using hematoxylin and eosin staining. Expression levels of adiponectin (APN), high-sensitivity C-reactive protein (hs-CRP), and neurotrophin-4 (NT-4) in each group was detected using immunohistochemistry, PCR, Western blotting, and ELISA, respectively. RESULTS: A stable transgenic cell line of LIF-hUCMSCs was constructed. F-ERG and FITC-dextran examinations revealed no abnormalities of retinal structure and function in group A, severe damage of the retinal blood vessels and function in group B, and improved retinal structure and function in group C and especially group D. qPCR, ELISA, and Western blot analyses revealed progressively higher APN and NT-4 expression levels in groups B, C, and D than in group A. hs-CRP expression was significantly higher in group B than in groups A, C, and D, and was significantly higher in group C than in group D (P<0.05). CONCLUSION: LIF-hUCMSCs protect the retina of diabetic rats by upregulating APN and NT-4 expression and downregulating hs-CRP expression in the retina.