In recent years, there has been a captivating focus of interest in elucidating the intricate crosstalk between adiponectin (APN), a versatile fat-associated adipokine and ocular pathologies. Unveiling the intricate relationship between adipocytokine APN and its receptors (AdipoRs) with aging eye disorders has emerged as a fascinating frontier in medical research. This review article delves into this connection, illuminating the hidden influence of APN on retinal health. This comprehensive review critically examines the latest findings and breakthroughs that underscore the pivotal roles of APN/AdipoRs signaling in maintaining ocular homeostasis and protecting against eye ailments. Here, we meticulously explore the intriguing mechanisms by which APN protein influences retinal function and overall visual acuity. Drawing from an extensive array of cutting-edge studies, the article highlights APN\'s multifaceted functions, ranging from anti-inflammatory properties and oxidative stress reduction to angiogenic regulation within retinal and macula tissues. The involvement of APN/AdipoRs in mediating these effects opens up novel avenues for potential therapeutic interventions targeting prevalent aging eye conditions. Moreover, this review unravels the interplay between APN signaling pathways and age-related macular degeneration (AMD). The single-cell RNA-seq results validate the expression of both the receptor isoforms (AdipoR1/R2) in retinal cells. The transcriptomic analysis showed lower expression of AdipoR1/2 in dry AMD pathogenesis compared to healthy subjects. The inhibitory adiponectin peptide (APN1) demonstrated over 75% suppression of CNV, whereas the control peptide did not exert any inhibitory effect on choroidal neovascularization (CNV). The elucidation of these relationships fosters a deeper understanding of adipose tissue\'s profound influence on ocular health, presenting new prospects for personalized treatments and preventative measures. Because APN1 inhibits CNV and leakage, it can be used to treat human AMD, although the possibility to treat human AMD is in the early stage and more clinical research is needed. In conclusion, this review provides a captivating journey into the enthralling world of APN, intertwining the realms of adipose biology and ophthalmology in aging.

In the pathogenesis of age-related macular degeneration, long non-coding RNAs have become important regulators. This study aimed to investigate the role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in the progression of choroidal neovascularization (CNV) and the underlying mechanisms. The in vivo and in vitro model of CNV was established using laser-induced mouse CNV model and human choroidal vascular endothelial cells (HCVECs) exposed to hypoxia respectively. We explore the role of MALAT1 in the pathogenesis of CNV by using the small interference RNA both in vivo and in vitro. MALAT1 expression was found to be upregulated in the retinal pigment epithelial-choroidal complexes. MALAT1 knockdown inhibited CNV development and leakage in vivo and decreased HCVECs proliferation, migration, and tube formation in vitro. MALAT1 performed the task as a miR-17-5p sponge to regulate the expression of vascular endothelial growth factor A (VEGFA) and E26 transformation specific-1 (ETS1). This study provides a new perspective on the pathogenesis of CNV and suggests that the axis MALAT/miR-17-5p/VEGFA or ETS1 may be an effective therapeutic target for CNV.

Age-related changes in vitreous molecular and anatomic morphology begin early in life and involve two major processes: vitreous liquefaction and weakening of vitreo-retinal adhesion. An imbalance in these two processes results in anomalous posterior vitreous detachment (PVD), which comprises, among other conditions, vitreo-macular adhesion (VMA) and traction (VMT). VMA is more common in patients with neovascular age-related macular degeneration (nAMD) than age-matched control patients, with the site of posterior vitreous adherence to the inner retina correlating with location of neovascular complexes. The pernicious effects of an attached posterior vitreous on age-related macular degeneration (AMD) progression involve mechanical forces, enhanced fluid influx and inflammation in and between the retinal layers, hypoxia leading to an accumulation of vascular endothelial growth factor (VEGF) and other stimulatory cytokines, and probably an infiltration of hyalocytes. It has been shown that vitrectomy not only mitigates progression to end-stage AMD, but existing choroidal neovascularization regresses after surgery. Thus, surgical PVD induction during vitrectomy or by pharmacologic vitreolysis may be considered in non-responders to anti-VEGF treatment with concomitant VMA.
UNASSIGNED: Altersbedingte Veränderungen der molekularen und anatomischen Morphologie des Glaskörpers beginnen schon früh im Leben und umfassen 2 Hauptprozesse: die Glaskörperverflüssigung und die Schwächung der vitreoretinalen Adhäsion. Ein Ungleichgewicht zwischen diesen beiden Prozessen führt zu einer anomalen hinteren Glaskörperabhebung (HGA), die unter anderem die vitreomakuläre Adhäsion (VMA) und Traktion (VMT) umfasst. VMA tritt bei Patienten mit neovaskulärer altersabhängiger Makuladegeneration (nAMD) häufiger auf als bei altersgleichen Kontrollpatienten, wobei die Stelle, an der der hintere Glaskörper an der inneren Netzhaut haftet, mit der Lage des neovaskulären Komplexes korreliert. Die schädlichen Auswirkungen eines anhaftenden hinteren Glaskörpers auf die Progression der altersabhängigen Makuladegeneration (AMD) umfassen mechanische Kräfte, einen verstärkten Flüssigkeitseinstrom und Inflammation in und zwischen den Netzhautschichten, Hypoxie, die zu einer Akkumulation von „vascular endothelial growth factor“ (VEGF) und anderen stimulierenden Zytokinen führt, und wahrscheinlich auch eine Infiltration von Hyalozyten. Es hat sich gezeigt, dass eine Vitrektomie nicht nur das Fortschreiten der AMD im Endstadium aufhält, sondern auch dass sich bestehende chorioidale Neovaskularisationen nach der Operation zurückbilden. Daher kann eine chirurgische HGA-Induktion im Rahmen der Vitrektomie oder durch pharmakologische Vitreolyse bei Nichtansprechen auf die Anti-VEGF-Behandlung und gleichzeitig vorliegender VMA in Betracht gezogen werden.

Retinal angiomatous proliferation (RAP) and other types of choroidal neovascularization (CNV) are very rarely reported in patients with retinitis pigmentosa (RP). We present a case report of a 91-year-old patient with an obvious RP phenotype, who presented with a sudden onset of vision worsening and metamorphopsia in the left eye. Genetic testing on the UK inherited retinal disease panel did not identify a pathogenic variant. Multimodal imaging comprising optical coherence tomography (OCT), OCT angiography, and fluorescein and indocyanine green angiography showed a RAP lesion in the left macula. The patient received three treatments of monthly injections of aflibercept, with excellent morphological and functional outcomes. Taking into account the patient\'s age at presentation of the RAP lesion, it is not clear whether the RAP was associated or coincidental with RP. This case report highlights the importance of possessing an awareness that RAP lesions can occur in RP. Moreover, due to a good response and potential safety concerns with continuous anti-VEGF injections in RP patients, a pro re nata (PRN) regimen might be the safest option.

Age-related macular degeneration (AMD), a leading cause of irreversible blindness in adults, may result in poor central vision, making it difficult to see, read, and drive. AMD is generally classified in either dry or wet types. Milder cases of dry AMD may progress to geographic atrophy (GA), leading to significant visual disability; wet, or neovascular AMD, which involves choroidal neovascularization (CNV), can lead to complete loss of central vision. Adiponectin (APN) discovery in the mid-1990\'s and, subsequently, its two cognate receptors (AdipoRs) in the early 2000s have led to a remarkable progress in better understanding metabolic disorders, as well as metabolism-associated ocular pathology. APN/AdipoRs signaling plays a central role in a variety of molecular and cellular physiological events, including glucose and lipid metabolism, whole-body energy regulation, immune and inflammation responses, insulin sensitivity and retinal cell biological functions. This review is an amalgamation of recent information related to APN/AdipoRs in the pathophysiology of retinal diseases and furthers its association with AMD and diabetic retinopathy. Additionally, we present our original research, where we designed control peptide and CNV inhibitory peptide from the globular region of APN to see the effect of these peptides on the mouse model of laser-induced CNV. The inhibitory peptide (APN1) inhibited CNV by more than 75% while the control peptide did not inhibit CNV.

To investigate the molecular mechanism underlying the onset of choroidal neovascularization (CNV).
Integrated transcriptomic and proteomic analyses of retinas in mice with laser-induced CNV were performed using RNA sequencing and tandem mass tag. In addition, the laser-treated mice received systemic interferon-β (IFN-β) therapy. Measurements of CNV lesions were acquired by the confocal analysis of stained choroidal flat mounts. The proportions of T helper 17 (Th17) cells were determined by flow cytometric analysis.
A total of differentially expressed 186 genes (120 up-regulated and 66 down-regulated) and 104 proteins (73 up-regulated and 31 down-regulated) were identified. The gene ontology and KEGG pathway analyses indicated that CNV was mainly associated with immune and inflammatory responses, such as cellular response to IFN-β and Th17 cell differentiation. Moreover, the key nodes of the protein-protein interaction network mainly involved up-regulated proteins, including alpha A crystallin and fibroblast growth factor 2, and were verified by Western blotting. To confirm the changes in gene expression, real-time quantitative PCR was performed. Furthermore, levels of IFN-β in both the retina and plasma, as measured by enzyme-linked immunosorbent assay (ELISA), were significantly lower in the CNV group than in the control group. IFN-β treatment significantly reduced CNV lesion size and promoted the proliferation of Th17 cells in laser-treated mice.
This study demonstrates that the occurrence of CNV might be associated with the dysfunction of immune and inflammatory processes and that IFN-β could serve as a potential therapeutic target.

OBJECTIVE: This study aims to investigate the cytokines profiling in the aqueous humor of patients with polypoidal choroidal vasculopathy (PCV) before and after intravitreal ranibizumab injection (IVR).
METHODS: 14 patients clinically diagnosed with PCV and 15 cataract patients of similar age and gender (control group) were included. Throughout the cataract surgery and IVR, aqueous humor samples were collected from the PCV and control groups.
RESULTS: The levels of macrophage inflammatory protein 1β (MIP-1β) and normal T cell expressed and secreted (RANTES) in PCV patients were significantly lower than control subjects (P=0.045 and P=0.004, respectively). The concentration of vascular endothelial growth factor-A (VEGF-A) was significantly higher than the control group (P=0.003). The level of MIP-1β was greatly increased in PCV patients compared to prior to IVR (P=0.001). After IVR, the level of VEGF-A in PCV patients were considerably lower compared to before IVR (P=0.001). There was no link between the expression of several cytokines (MCP-1, MIP-1, Eotaxin, G-CSF, IL-8, IL-6, IL-5, IP-10 and IFN-γ) in the aqueous humor of PCV patients before and after intravitreal ranibizumab injection (IVR). The association between IL-5 expression and central macular thickness (CMT) was discovered before IVR (P=0.02), however, the correlation between several cytokines (MCP-1, MIP-1, Eotaxin, G-CSF, IL-8, IL-6, IL-5, IP-10 and IFN-γ) was discovered in PCV patients after IVR.
CONCLUSIONS: Based on our findings, we discovered that the production of neovascularization in PCV patients is driven by both angiogenic and inflammatory factors, with a correlation seen between several cytokines.

UNASSIGNED: Age-related macular degeneration (AMD) is the leading cause of blindness, and is associated with oxidative stress and the development of new blood vessels. At present, the main clinical treatment for AMD includes intraocular injection of vascular endothelial growth factor (VEGF). However, treatment includes repeated injections with significant side-effects. Therefore, new treatment options are required. The aim of the present study was to discover the new treatment target of AMD from the gene level.
UNASSIGNED: The Gene Expression Omnibus (GEO) database was used to analyze the differential gene expression in AMD, and the regulator of G-protein signaling 1 (RGS1) was obtained by bioassay. Western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to detect the expression levels of RGS1, VEGF, and other related molecules in human microvascular endothelial cells (HMECs) under different conditions. Cell viability, apoptosis, and proliferation of HMECs were measured by Cell Counting Kit-8 proliferation assay. Immunofluorescence and immunohistochemistry detected the interaction between RGS1, platelet endothelial cell adhesion molecule-1, and VEGF.
UNASSIGNED: RGS1 was found to closely associated with the proliferation of vascular endothelial cells, and therefore, with angiogenesis. The expression of RGS1, VEGF, and platelet endothelial cell adhesion molecule-1 was upregulated in laser model mice and hypoxia model HMECs. Knockout of RGS1 inhibits the expression of VEGF and HMEC proliferation, thereby inhibiting AMD angiogenesis.
UNASSIGNED: Our results support the use of RGS1 as a new potential target for the future treatment of AMD.

OBJECTIVE: To report two cases of laser-induced choroidal neovascularization (CNV) using swept source optical coherence tomography (SS-OCTA) imaging in patients with proliferative diabetic retinopathy.
METHODS: Two patients developed CNV adjacent to laser scars, and these neovascular lesions were detected on SS-OCTA imaging. Historically, both patients had subretinal fluid associated with these lesions. Visual acuity for both patients was 20/25 in the affected eyes. Both patients were observed over multiple years with stable CNV and visual acuity.
CONCLUSIONS: SS-OCTA was able to detect laser-induced CNV in a rapid and non-invasive manner. When there is no foveal involvement and excellent visual acuity, we recommend close observation since the CNV may not progress.

Immunosenescence is considered a possible factor in the development of age-related macular degeneration and choroidal neovascularization (CNV). However, age-related changes of myeloid cells (MCs), such as microglia and macrophages, in the healthy retina or during CNV formation are ill-defined. In this study, Cx3cr1-positive MCs were isolated by fluorescence-activated cell sorting from six-week (young) and two-year-old (old) Cx3cr1GFP/+ mice, both during physiological aging and laser-induced CNV development. High-throughput RNA-sequencing was performed to define the age-dependent transcriptional differences in MCs during physiological aging and CNV development, complemented by immunohistochemical characterization and the quantification of MCs, as well as CNV size measurements. These analyses revealed that myeloid cells change their transcriptional profile during both aging and CNV development. In the steady state, senescent MCs demonstrated an upregulation of factors contributing to cell proliferation and chemotaxis, such as Cxcl13 and Cxcl14, as well as the downregulation of microglial signature genes. During CNV formation, aged myeloid cells revealed a significant upregulation of angiogenic factors such as Arg1 and Lrg1 concomitant with significantly enlarged CNV and an increased accumulation of MCs in aged mice in comparison to young mice. Future studies need to clarify whether this observation is an epiphenomenon or a causal relationship to determine the role of immunosenescence in CNV formation.