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To review the basic principles of ultra-widefield fundus autofluorescence (UWF-FAF) and discuss its clinical application for a variety of retinal and choroidal disorders. A systematic review of the PubMed database was performed using the search terms “ultra-widefield,” “autofluorescence,” “retinal disease” and “choroidal disease.” UWF-FAF imaging is a recently developed noninvasive retinal imaging modality with a wide imaging range that can locate peripheral fundus lesions that traditional fundus autofluorescence cannot. Multiple commercially available ultra-widefield imaging systems, including Heidelberg Spectralis and Optomap Ultra-Widefield systems, are available to the clinician. Imaging by UWF-FAF is more comprehensive; it can reflect the content and distribution of the predominant ocular fluorophore in retinal pigment epithelial cells and evaluate the metabolic status of RPE of various retinal and choroidal disorders. UWF-FAF can detect abnormalities that traditional fundus autofluorescence cannot; therefore, it can be used to better elucidate disease pathogenesis, analyze genotype–phenotype correlations, diagnose and monitor disease.

Identification of key regulators of energy homeostasis holds important therapeutic promise for metabolic disorders, such as obesity and diabetes. ACE2 cleaves angiotensin II (Ang II) to generate Ang-(1-7) which acts mainly through the Mas1 receptor. Here, we identify ACE2 pathway as a critical regulator in the maintenance of thermogenesis and energy expenditure. We found that ACE2 is highly expressed in brown adipose tissue (BAT) and that cold stimulation increases ACE2 and Ang-(1-7) levels in BAT and serum. Ace2 knockout mice (Ace2-/y) and Mas1 knockout mice (Mas1-/-) displayed impaired thermogenesis. Mice transplanted with brown adipose tissue from Mas1-/- display metabolic abnormalities consistent with those seen in the Ace2 and Mas1 knockout mice. In contrast, impaired thermogenesis of Leprdb/db obese diabetic mice and high-fat diet-induced obese mice were ameliorated by overexpression of Ace2 or continuous infusion of Ang-(1-7). Activation of ACE2 pathway was associated with improvement of metabolic parameters, including blood glucose, lipids, and energy expenditure in multiple animal models. Consistently, ACE2 pathway remarkably enhanced the browning of white adipose tissue. Mechanistically, we showed that ACE2 pathway activated Akt/FoxO1 and PKA pathway, leading to induction of UCP1 and activation of mitochondrial function. Our data propose that adaptive thermogenesis requires regulation of ACE2 pathway and highlight novel potential therapeutic targets for the treatment of metabolic disorders.

PURPOSE To determine the relationship between large-sized and medium-sized choroidal vessels and choriocapillaris using the three-dimensional choroidal vascularity index (3D CVI) and percentage of flow deficits (FD%). METHODS Prospective observational study. The main outcome measures included choroidal volume parameters (3D CVI, mean choroidal thickness, total choroidal volume, choroidal luminal volume, and choroidal stromal volume), choriocapillaris parameters (FD%, average area of FD, and FD count), and age and axial length. RESULTS A total of 63 healthy individuals with an average age of 40.60 ± 12.32 years were included in this study. Univariate analysis showed that FD% (R = 0.295, P = 0.019) and area of FD (R = 0.276, P = 0.028) were significantly positively associated with 3D CVI, and FD count was negatively associated with 3D CVI (R = -0.297, P = 0.018). After adjusting for age and axial length, a significant correlation between FD% and 3D CVI (R = 0.264, P = 0.039) and between area of FD and 3D CVI remained (R = 0.267, P = 0.037). However, no significant correlation was found between FD count and 3D CVI after adjusting for axial length (R = -0.220, P = 0.085). CONCLUSION In healthy individuals, choroidal vessel dilatation as suggested by elevated 3D CVI may lead to decreased choriocapillaris perfusion, which was correlated with an enlarged area of FD in choriocapillaris.

To investigate the effect of P2 receptor on microglia and its inhibitor PPADS on choroidal neovascularization. Forty CX3CR1GFP/+ mice were randomly divided into 8 groups. In addition to the normal group, the rest of groups were receiving laser treatment. The retina and choroid from the second, third, fourth and fifth group of mice were taken in the 1, 4, 7, 14 days after laser treatment. The mice in the sixth and seventh group received intravitreal injection of 2 µl PPADS or PBS respectively immediately after laser treatment. The mice in the eighth group received topical application of PPADS once per day of three days. The mice in sixth, seventh and eighth group received AF and FFA examination on the fourth day after laser treatment. Immunofluorescence histochemical staining and real-time quantitative PCR were used to evaluate P2 expression and its effect on choroidal neovascularization. After laser treatment, activated microglia can express P2 receptors (P2X4, P2X7, P2Y2 and P2Y12). The expression of P2 increased on the first day after laser damage, peaked on the fourth day (tP2X4 = 6.05, tP2X7 = 2.95, tP2Y2 = 3.67, tP2Y12 = 5.98, all P P2X4 = 5.54, tP2X7 = 9.82, tP2Y2 = 3.86, tP2Y12 = 7.91, all P P2X4 = 3.24, tP2X7 = 5.89, tP2Y2 = 6.75, tP2Y12 = 4.97, all P

To investigate the relationship between leakage index on ultra-widefield fluorescence angiography (UWFFA) in different regions of retina and its correlation with cystoid macular edema (CME) in central retinal vein occlusion (CRVO) eyes. Patients with naive non-ischemic CRVO that had undergone UWFFA were identified. UWFFA images in the late phase were used to analyze the leakage index, which was performed by a semi-automatic method using ImageJ. The UWFFA images were subdivided into four regions by concentric circles centered on the macula for analysis. Optical coherence tomography (OCT) images were used to identify the presence of CME and obtain central macular thickness (CMT). A total of 57 eyes from 57 CRVO patients were analyzed in this study, including 43 eyes with CME and 14 eyes without CME. The leakage index in panretinal, peri-macular area (PMA), and near-peripheral area (NPA) was significantly different between eyes with CME and eyes without CME. Leakage index of PMA, NPA, mid-peripheral area (MPA), and panretinal area was significantly correlated with CMT, particularly the PMA. The distribution of leakage is different between patients with CME and patients without CME. The contribution of leakage index in different regions to CME was different, most predominant in PMA and NPA, and the closer to the center of the macula, the stronger the correlation between leakage index and CMT. A linear correlation was observed between CMT and the leakage index of panretinal area and all regions except far-peripheral area (FPA).

Purpose The appearance of the far peripheral retina in normal eyes was observed using an Optos ultra-wide field fluorescein angiography imaging system. Methods A cross-sectional study of ultra-wide field pseudocolor and angiography images obtained using the Optos 200Tx. Four different non-vascular and six vascular-associated fluorescence features in far peripheral retina were analyzed. Results A total of 166 eyes in 83 patients met the inclusion criteria. The mean patient age was 40.78 ± 10.94 years (range: 20–65 years) with a female-to-male ratio of 0.98. Slight cataract were present in 64 eyes (38.55%), low to moderate myopia in 50 eyes (30.12%), and unspecified visual disturbances in 52 eyes (31.33%). Far peripheral retinas were found to have mottled florescent band in 42.17% eyes, ground glass hyperfluorescence in 84.34% eyes, granular hyperfluorescence in 12.65% eyes, local mottled fluorescence in 10.84% eyes, vascular anastomosis with a peripheral avascular area in 36.23% eyes, invisible capillary details in 50.67% eyes, vessels passing through the ora serrata in 16.98% eyes, late-phase slight leakage in 32.53% eyes, angiectasis in 18.67% eyes, and microaneurysm in 34.94% eyes. Conclusion Ultra-wide field fluorescein angiography revealed various fluorescence features in the periphery of normal eyes, providing a basis for interpreting normal and pathological changes in peripheral retina and an important reference for clinical work.

Elevated circulating adipocyte fatty acid-binding protein (AFABP) levels have been found to correlate with diabetic nephropathy staging in cross-sectional studies. However, it remains unclear whether these higher serum levels reflect a role of AFABP in the development of diabetic kidney disease (DKD), or simply result from its impaired renal clearance in DKD. Here we investigated prospectively the prognostic importance of serum AFABP level in the development of adverse renal outcomes in a large clinic-based cohort of participants with type 2 diabetes. Baseline serum AFABP levels were measured in 5454 Chinese participants from the Hong Kong West Diabetes Registry. The association between circulating AFABP levels and incident adverse renal outcomes—defined as a composite endpoint of a sustained 40% decline in eGFR, end-stage renal disease requiring renal replacement therapy or kidney transplantation, or renal deaths—was evaluated using multivariable Cox regression analysis. Over a median follow-up of 5 years, 754 of the 5454 participants developed incident adverse renal outcomes. Elevated circulating AFABP levels were independently associated with incident adverse renal outcomes (HR 1.43, 95% CI 1.31, 1.57, p

Adiponectin, one of the most abundant adipose-derived hormones, has variable actions in many tissues and organs. Although principally known for its insulin-sensitizing activity, recent data also highlight its homeostatic function, which is mediated both by direct actions on metabolic cells and indirectly through immunomodulatory effects on immune cells. Here we review the multifaceted immunometabolic actions of adiponectin and attempt to unify some of the contradictory reports on adiponectin function in inflammatory processes. We propose that a holistic understanding of adiponectin function can be garnered only from understanding its actions both on the immune system and on metabolism.

Although leptin is a key adipokine promoting liver fibrosis, adiponectin may prevent liver injury. To determine the role of these adipokines in liver fibrosis and to understand their expression in vivo, fa/fa rats and their lean littermates were subjected to bile duct ligation (BDL). Histomorphometry for collagen and alpha-smooth muscle actin (alpha-SMA) revealed that lean rats, but not fa/fa littermates, had significant fibrosis with abundant hepatic stellate cell (HSC) activation. The lean-BDL rats had significantly higher leptin concentrations in the hepatic vein than lean sham-operated, fa/fa BDL, or fa/fa sham-operated rats. Co-localization of leptin and alpha-SMA in activated HSCs was observed by immunohistochemistry. Real-time reverse transcriptase-polymerase chain reaction and Western blot analysis confirmed the presence of leptin and alpha-SMA in activated, but not quiescent, HSCs, whereas only quiescent HSCs synthesized adiponectin mRNA and protein. Adiponectin overexpression in activated HSCs reduced proliferation, augmented apoptosis, and reduced expression of alpha-SMA and proliferating cell nuclear antigen. Adiponectin receptors (AdipoR1 and AdipoR2) were detected in both activated and quiescent HSCs, but only activated HSCs produced significant apoptosis after treatment with either globular or full-length adiponectin. Adiponectin may act to reverse HSC activation, maintain HSC quiescence, or significantly, may have important therapeutic implications in liver fibrosis.