Singh RB, Perepelkina T, Testi I, Young BK, Mirza T, Invernizzi A, Biswas J, Agarwal A. Imaging-based Assessment of Choriocapillaris: A Comprehensive Review. Semin Ophthalmol 2022;:1-22.Abstract
PURPOSE: Over the past two decades, advancements in imaging modalities have significantly evolved the diagnosis and management of retinal diseases. Through these novel platforms, we have developed a deeper understanding of the anatomy of the choroidal vasculature and the choriocapillaris. The recently developed tools such as optical coherence tomography (OCT) and OCT angiography (OCTA) have helped elucidate the pathological mechanisms of several posterior segment diseases. In this review, we have explained the anatomy of the choriocapillaris and its close relationship to the outer retina and retinal pigment epithelium. METHODS: A comprehensive search of medical literature was performed through the Medline/PubMed database using search terms: choriocapillaris, choroid, quantification, biomarkers, diabetic retinopathy, age-related macular degeneration, choroidal blood flow, mean blur rate, flow deficit, optical coherence tomography, optical coherence tomography angiography, fluorescein angiography, indocyanine green angiography, OCTA, Doppler imaging, uveitis, choroiditis, white dot syndrome, tubercular serpiginous-like choroiditis, choroidal granuloma, pachychoroid, toxoplasmosis, central serous chorioretinopathy, multifocal choroiditis, choroidal neovascularization, choroidal thickness, choroidal vascularity index, choroidal vascular density, and choroidal blood supply. The search terms were used either independently or combined with choriocapillaris/choroid. RESULTS: The imaging techniques which are used to qualitatively and quantitatively analyze choriocapillaris are described. The pathological alterations in the choriocapillaris in an array of conditions such as diabetes mellitus, age-related macular degeneration, pachychoroid spectrum of diseases, and inflammatory disorders have been comprehensively reviewed. The future directions in the study of choriocapillaris have also been discussed. CONCLUSION: The development of imaging tools such as OCT and OCTA has dramatically improved the assessment of choriocapillaris in health and disease. The choriocapillaris can be delineated from the stromal choroid using the OCT and quantified by manual or automated methods. However, these techniques have inherent limitations due to the lack of an anatomical distinction between the choriocapillaris and the stromal choroid, which can be overcome with the use of predefined segmentation slabs on OCT and OCTA. These segmentation slabs help in standardizing the choriocapillaris imaging and obtain repeatable measurements in various conditions such as diabetic retinopathy, age-related macular degeneration, pachychoroid spectrum, and ocular inflammations. Additionally, Doppler imaging has also been effectively used to evaluate the choroidal blood flow and quantifying the choriocapillaris and establishing its role in the pathogenesis of various retinochoroidal diseases. As tremendous technological advancements such as wide-field and ultra-wide field imaging take place, there will be a significant improvement in the ease and accuracy of quantifying the choriocapillaris.
Patel NA, Acaba-Berrocal LA, Hoyek S, Fan KC, Martinez-Castellanos MA, Baumal CR, Harper AC, Berrocal AM, of (ROPIC) RPIC. Practice Patterns and Outcomes of Intravitreal Anti-VEGF Injection for Retinopathy of Prematurity - An International Multicenter Study. Ophthalmology 2022;Abstract
PURPOSE: To report practice patterns of intravitreal injections of anti-Vascular Endothelial Growth Factor (VEGF) for Retinopathy of Prematurity (ROP) and outcomes data with a focus on retreatments and complications. DESIGN: Multicenter, international, retrospective, consecutive series. SUBJECTS: Patients with ROP treated with anti-VEGF injections from 2007 to 2021. METHODS: Twenty-three sites (16 Unites States [US] and 7 non-US sites) participated. Data collected included demographics, birth characteristics, exam findings, and methods of injections. Comparisons between US and non-US sites were made. MAIN OUTCOME MEASURES: Primary outcomes included number and types of retreatments as well as complications. Secondary outcomes included specifics of the injection protocols including types of medication, doses, distance from limbus, use of antibiotics, and quadrants where injections were delivered. RESULTS: A total of 1677 eyes of 918 patients (43% females, 57% males) were included. Mean gestational age was 25.7 weeks (range 21.2-41.5), and mean birth weight was 787 g (range 300-2,700). Overall, a 30 G needle was most commonly utilized (51%) and the quadrant injected was most frequently the inferior-temporal (51.3%). The distance from the limbus ranged from 0.75 to 2 mm, 1 mm being the most common (65%). Bevacizumab was the most common anti-VEGF (71.4%), with a dose of 0.625 mg in 64% of cases. Overall, 604 (36%) of eyes required retreatment. Of those, 79.8% were retreated with laser alone, 10.6% with anti-VEGF injection alone, and 9.6% with combined laser and injection. Complications following anti-VEGF injections occurred in 15 (0.9%) eyes and no cases of endophthalmitis were reported. Patients in the US had lower birth weights and gestational ages (665.6 g and 24.5 weeks, respectively) compared to non-US patients (912.7 g and 26.9 weeks, respectively) (p<0.0001). Retreatment with reinjection and laser was significantly more common in the US compared to the non-US group (8.5% vs 4.7% [p=0.0016] and 55% vs 7.2% [p<0.001], respectively). There was no difference in the incidence of complications between the two geographical subgroups. CONCLUSION: Anti-VEGF injections for ROP were safe and well tolerated despite a variance in practice patterns. Infants with ROP receiving injections in the United States tended to be younger, smaller, and were treated earlier with more re-treatments than non-United States neonates with ROP.
Kozycki CT, Kodati S, Huryn L, Wang H, Warner BM, Jani P, Hammoud D, Abu-Asab MS, Jittayasothorn Y, Mattapallil MJ, Tsai WL, Ullah E, Zhou P, Tian X, Soldatos A, Moutsopoulos N, Kao-Hsieh M, Heller T, Cowen EW, Lee C-CR, Toro C, Kalsi S, Khavandgar Z, Baer A, Beach M, Long Priel D, Nehrebecky M, Rosenzweig S, Romeo T, Deuitch N, Brenchley L, Pelayo E, Zein W, Sen N, Yang AH, Farley G, Sweetser DA, Briere L, Yang J, de Oliveira Poswar F, Schwartz I, Silva Alves T, Dusser P, Koné-Paut I, Touitou I, Titah SM, van Hagen PM, van Wijck RTA, van der Spek PJ, Yano H, Benneche A, Apalset EM, Jansson RW, Caspi RR, Kuhns DB, Gadina M, Takada H, Ida H, Nishikomori R, Verrecchia E, Sangiorgi E, Manna R, Brooks BP, Sobrin L, Hufnagel R, Beck D, Shao F, Ombrello AK, Aksentijevich I, Kastner DL, Kastner DL. Gain-of-function mutations in ALPK1 cause an NF-κB-mediated autoinflammatory disease: functional assessment, clinical phenotyping and disease course of patients with ROSAH syndrome. Ann Rheum Dis 2022;Abstract
OBJECTIVES: To test the hypothesis that ROSAH (retinal dystrophy, optic nerve oedema, splenomegaly, anhidrosis and headache) syndrome, caused by dominant mutation in ALPK1, is an autoinflammatory disease. METHODS: This cohort study systematically evaluated 27 patients with ROSAH syndrome for inflammatory features and investigated the effect of ALPK1 mutations on immune signalling. Clinical, immunologic and radiographical examinations were performed, and 10 patients were empirically initiated on anticytokine therapy and monitored. Exome sequencing was used to identify a new pathogenic variant. Cytokine profiling, transcriptomics, immunoblotting and knock-in mice were used to assess the impact of ALPK1 mutations on protein function and immune signalling. RESULTS: The majority of the cohort carried the p.Thr237Met mutation but we also identified a new ROSAH-associated mutation, p.Tyr254Cys.Nearly all patients exhibited at least one feature consistent with inflammation including recurrent fever, headaches with meningeal enhancement and premature basal ganglia/brainstem mineralisation on MRI, deforming arthritis and AA amyloidosis. However, there was significant phenotypic variation, even within families and some adults lacked functional visual deficits. While anti-TNF and anti-IL-1 therapies suppressed systemic inflammation and improved quality of life, anti-IL-6 (tocilizumab) was the only anticytokine therapy that improved intraocular inflammation (two of two patients).Patients' primary samples and in vitro assays with mutated ALPK1 constructs showed immune activation with increased NF-κB signalling, STAT1 phosphorylation and interferon gene expression signature. Knock-in mice with the Alpk1 T237M mutation exhibited subclinical inflammation.Clinical features not conventionally attributed to inflammation were also common in the cohort and included short dental roots, enamel defects and decreased salivary flow. CONCLUSION: ROSAH syndrome is an autoinflammatory disease caused by gain-of-function mutations in ALPK1 and some features of disease are amenable to immunomodulatory therapy.
Dong L, Han H, Huang X, Ma G, Fang D, Qi H, Han Z, Wang L, Tian J, Vanhaesebroeck B, Zhang G, Zhang S, Lei H. Idelalisib inhibits experimental proliferative vitroretinopathy. Lab Invest 2022;Abstract
Proliferative vitreoretinopathy (PVR) is a fibrotic eye disease that develops after rhegmatogenous retinal detachment surgery and open-globe traumatic injury. Idelalisib is a specific inhibitor of phosphoinositide 3-kinase (PI3K) δ. While PI3Kδ is primarily expressed in leukocytes, its expression is also considerably high in retinal pigment epithelial (RPE) cells, which play a crucial part in the PVR pathogenesis. Herein we show that GeoMx Digital Spatial Profiling uncovered strong expression of fibronectin in RPE cells within epiretinal membranes from patients with PVR, and that idelalisib (10 μM) inhibited Akt activation, fibronectin expression and collagen gel contraction induced by transforming growth factor (TGF)-β2 in human RPE cells. Furthermore, we discovered that idelalisib at a vitreal concentration of 10 μM, a non-toxic dose to the retina, prevented experimental PVR induced by intravitreally injected RPE cells in rabbits assessed by experienced ophthalmologists using an indirect ophthalmoscope plus a + 30 D fundus lens, electroretinography, optical coherence tomography and histological analysis. These data suggested idelalisib could be harnessed for preventing patients from PVR.
Hoyek S, Wang M, Berrocal AM, Wong A, Place EM, Mason-Suares H, Lin AE, Mukai S, Patel NA. Combined X-linked familial exudative vitreoretinopathy and retinopathy of prematurity phenotype in an infant with mosaic turner syndrome with ring X chromosome. Ophthalmic Genet 2022;:1-6.Abstract
BACKGROUND: Retinopathy of prematurity (ROP) and familial exudative vitreoretinopathy (FEVR) are two distinct pathologies of retinal angiogenesis with overlapping clinical features. METHODS: Examination, multimodal imaging, and genetic testing were used to guide diagnosis and treatment. RESULTS: We report a combined phenotype of X-linked FEVR and ROP in a 4-month-old girl with mosaic Turner syndrome with ring X chromosome born at 26 weeks gestational age. She was initially diagnosed with atypical ROP with a vitreous band causing a localized traction retinal detachment, inferotemporal to the macula in the right eye, vessels to posterior zone 2 with no clear ridge temporally in the left eye, and fluorescein leakage in both eyes. Due to the suspicion of concurrent FEVR, genetic testing using a vitreoretinopathy panel was performed which revealed a mosaic Turner syndrome associated with 45,X/46,X,r(X), subsequently confirmed by chromosome analysis. The deleted region in the ring X chromosome included the NDP and RS1 genes. The patient was treated with laser photocoagulation of the peripheral avascular retina and sub-Tenon's triamcinolone injection in both eyes, intravitreal injection of bevacizumab in the left eye, and pars plicata vitrectomy in the right eye. CONCLUSIONS: In premature neonates with atypical ROP, a clinical suspicion of concurrent FEVR or similar vasculopathy is important and genetic testing may elucidate a genetic etiology, which could influence management and prognosis. Turner syndrome can be connected with co-occurring Mendelian gene disorders, particularly in individuals with mosaicism. The concurrence of FEVR and ROP appears to result in atypical and possibly more severe phenotypes.
Aleman TS, Huckfeldt RM, Serrano LW, Pearson DJ, Vergilio GK, McCague S, Marshall KA, Ashtari M, Doan TM, Weigel-DiFranco CA, Biron BS, Wen X-H, Chung DC, Liu E, Ferenchak K, Morgan JIW, Pierce EA, Eliott D, Bennett J, Comander J, Maguire AM. AAV2-hCHM Subretinal Delivery to the Macula in Choroideremia: Two Year Interim Results of an Ongoing Phase I/II Gene Therapy Trial. Ophthalmology 2022;Abstract
PURPOSE: To assess the safety of the subretinal delivery of a recombinant adeno-associated virus serotype 2 (AAV2) vector carrying a human CHM-encoding cDNA in choroideremia (CHM). DESIGN: Prospective, open-label, non-randomized, dose-escalation, phase 1/2 clinical trial. SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: Fifteen CHM patients (ages 20-57 years at dosing). METHODS, INTERVENTION, OR TESTING: Patients received uniocular subfoveal injections of low dose (up to 5x1010 vector genome (vg) per eye, n=5) or high dose (up to 1x1011 vg per eye, n=10) AAV2-hCHM. Patients were evaluated pre- and post-operatively for two years with ophthalmic examinations, multimodal retinal imaging and psychophysical testing. MAIN OUTCOME: Measures: visual acuity (VA), perimetry (10-2 protocol), spectral-domain optical coherence tomography (SD-OCT) and short-wavelength fundus autofluorescence (SW-FAF). RESULTS: We detected no vector-related or systemic toxicities. VA returned to within 15 letters of baseline in all but two patients (one developed acute foveal thinning, another patient, a macular hole); the rest showed no gross changes in foveal structure at two years. There were no significant differences between intervention and control eyes in mean light-adapted sensitivity by perimetry, or in the lateral extent of retinal pigment epithelium (RPE) relative preservation by SD-OCT and SW-FAF. Microperimetry showed non-significant (<3SD of the intervisit variability) gains in sensitivity in some locations and participants in the intervention eye. There were no obvious dose-dependent relationships. CONCLUSIONS: VA was within 15 letters of baseline after the subfoveal AAV2-hCHM injections in 13/15 (87%) of the patients. Acute foveal thinning with unchanged perifoveal function in one patient and macular hole in a second suggests foveal vulnerability to the subretinal injections. Longer observation intervals will help establish the significance of the minor differences in sensitivities and rate of disease progression observed between intervention and control eyes.
Bora K, Wang Z, Yemanyi F, Maurya M, Blomfield AK, Tomita Y, Chen J. Endothelial Cell Transcytosis Assay as an In Vitro Model to Evaluate Inner Blood-Retinal Barrier Permeability. J Vis Exp 2022;(184)Abstract
Dysfunction of the blood-retinal barrier (BRB) contributes to the pathophysiology of several vascular eye diseases, often resulting in retinal edema and subsequent vision loss. The inner blood-retinal barrier (iBRB) is mainly composed of retinal vascular endothelium with low permeability under physiological conditions. This feature of low permeability is tightly regulated and maintained by low rates of paracellular transport between adjacent retinal microvascular endothelial cells, as well as transcellular transport (transcytosis) through them. The assessment of retinal transcellular barrier permeability may provide fundamental insights into iBRB integrity in health and disease. In this study, we describe an endothelial cell (EC) transcytosis assay, as an in vitro model for evaluating iBRB permeability, using human retinal microvascular endothelial cells (HRMECs). This assay assesses the ability of HRMECs to transport transferrin and horseradish peroxidase (HRP) in receptor- and caveolae-mediated transcellular transport processes, respectively. Fully confluent HRMECs cultured on porous membrane were incubated with fluorescent-tagged transferrin (clathrin-dependent transcytosis) or HRP (caveolae-mediated transcytosis) to measure the levels of transferrin or HRP transferred to the bottom chamber, indicative of transcytosis levels across the EC monolayer. Wnt signaling, a known pathway regulating iBRB, was modulated to demonstrate the caveolae-mediated HRP-based transcytosis assay method. The EC transcytosis assay described here may provide a useful tool for investigating the molecular regulators of EC permeability and iBRB integrity in vascular pathologies and for screening drug delivery systems.
Sokol JT, Castillejos A, Sobrin L. Purtscher-like retinopathy following a bowel movement. Am J Ophthalmol Case Rep 2022;26:101560.Abstract
Purpose: To describe a case of Purtscher-like retinopathy that developed after a bowel movement. Observations: A 32-year-old male presented with blurry vision and bilateral temporal paracentral scotomas that developed immediately after standing up from a bowel movement. Fundoscopic examination was notable for bilateral cotton wool spots in the nasal macula. Optical coherence tomography showed bilateral intraretinal fluid, subfoveal fluid, and scattered areas of inner retinal hyperreflectivity and thickening corresponding to the areas of cotton wool spots on examination. No treatment was administered and the patient had significant improvement in symptoms 2 days later with resolution of macular edema. Conclusions: Here we report a case of Purtscher-like retinopathy after a bowel movement. Although the exact mechanism of Purtscher-like retinopathy is unknown, there are multiple reports of Purtscher-like retinopathy after extreme events involving Valsalva, such as during weightlifting, and we postulate that this presentation is likely of similar pathophysiology.
Zeng R, Garg I, Bannai D, Kasetty M, Katz R, Park J, Lizano P, Miller JB. Retinal microvasculature and vasoreactivity changes in hypertension using optical coherence tomography-angiography. Graefes Arch Clin Exp Ophthalmol 2022;Abstract
PURPOSE: To evaluate the retinal vasculature and vasoreactivity of patients with hypertension (HTN) using spectral domain optical coherence tomography angiography (SD-OCTA). METHODS: Patients with and without a diagnosis of HTN were included in this cross-sectional observational study. All eyes were imaged with SD-OCTA using 3 mm × 3 mm and 6 mm × 6 mm centered on both the fovea and optic disk. A second 6 mm × 6 mm scan was taken after a 30 s breath-hold. Vessel density (VD), vessel skeletonized density (VSD), and fractal dimension (FD) were calculated using customized MATLAB scripts. Vessel diameter index (VDI) was obtained by taking the ratio of VD to VSD. Vasoreactivity was measured by subtracting the VD or VSD before and after breath-hold (∆VD, ∆VSD). RESULTS: Twenty-three eyes with HTN (17 patients) and 17 control eyes (15 patients) were included. In the 6 mm × 6 mm angiogram centered on fovea, the superficial capillary plexus (SCP) VD (ß =  - 0.029, p = 0.012), VSD (ß =  - 0.004, p = 0.043) and the choriocapillaris VD (ß =  - 0.021, p = 0.030) were significantly decreased in HTN compared to control eyes. Similarly, FD was decreased in both the SCP (ß =  - 0.012, p = 0.013) and choriocapillaris (ß =  - 0.009, p = 0.030). In the 3 mm × 3 mm angiogram centered on optic disk, SCP VDI (ß =  - 0.364, p = 0.034) was decreased. ∆VD and ∆VSD were both reduced in the DCP (ß =  - 0.034, p = 0.032; ß =  - 0.013, p = 0.043) and ∆VSD was elevated in the choriocapillaris of HTN eyes (ß = 0.004, p = 0.032). CONCLUSIONS: The study used SD-OCTA to show significant differences in the retinal vasculature of hypertensive patients. It was also the first to demonstrate the potential of OCT-A to investigate retinal vascular reactivity in patients with HTN.
Wang F, Liu LQ, Liang RB, Zhang LJ, Shu HY, Liao XL, Pan YC, Wu J, Su T, Shao Y. Decreased Macular Retinal Thickness in Patients With Pterygium. Front Neurol 2022;13:881190.Abstract
Purpose: To explore alterations in macular retinal thickness (RT) and analyze correlation between macular RT and pterygium area, length in pterygium patients. Methods: Totally 13 patients with pterygium (left eye) and 13 healthy controls (left eye) were recruited. OCTA was applied to scan each eye to generate three-dimensional images. Based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method, each image was divided into nine subregions for the ETDRS: central (C); inner superior (IS); outer superior (OS); inner nasal (IN); outer nasal (ON); inner inferior (II); outer inferior (OI); inner temporal (IT); and outer temporal (OT). The macular RT in each subregion was measured. Furthermore, the correlation between RT and the area, length of pterygium was analyzed. Results: The visual acuity of pterygium patient was different from that of the control (P < 0.05). Besides, decreased intraretinal thickness of the IN and ON, increased intraretinal thickness of OT, decreased extraretinal thickness of OT, IN, ON, OS, and decreased retinal full layer thickness of medial superior, OS, IN, ON, and II subregions in pterygium group were observed. There was a negative correlation between RT of the IN and ON subregions and the length of pterygium (r = -0.5803 and r = -0.6013, P = 0.0376 and P = 0.0297). The RT of IN subregion was negatively correlated with pterygium area (r = -0.5844, P = 0.0359). According to the receiver operating characteristic analysis, in the ON subregion, the areas under the curve of the inner retinal thickness, outer retinal thickness and the whole retinal thickness were 1.0 (95% CI: 1.0), 0.882 (95% CI: 0.715 and 0.963), and 1.0 (95% CI: 1.0). The smallest area under the curve of retinal thickness in OT subregion was 0.018 (95% CI: 0-0.059). Conclusion: RT of pterygium patients was significantly decreased, and the main alterations occurred in the temporal side suggesting there might exist retinal structural alterations in pterygium.
Danford ID, Scruggs BA, Capone A, Trese MT, Drenser KA, Thanos A, Nudleman E, Amphornphruet A, Tipsuriyaporn B, Hubbard BG, Ells A, Harper AC, Goldstein J, Calvo C, Wallace-Carrete C, Berry D, Chang E, Leishman L, Shapiro M, Blair M, Mikhail M, Shields CL, Schwendeman R, Yonekawa Y, Gupta MP, Orlin A, Prakhunhungsit S, Mukai S, Berrocal A, Hartnett EM, Campbell PJ. The Prevalence of Retinal Disease and Associated Central Nervous System Disease in Young Patients with Incontinentia Pigmenti. Ophthalmol Retina 2022;Abstract
PURPOSE: To evaluate the prevalence of retinal disease on fluorescein angiography (FA) in patients with incontinentia pigmenti (IP) and to compare the severity of retinal disease in those with and without known central nervous system (CNS) disease. DESIGN: Multi-institutional consecutive retrospective case series SUBJECTS: New patients with a diagnosis of IP seen at the Casey Eye Institute, Oregon Health and Science University, Moran Eye Center, University of Utah, Wills Eye Hospital, or Bascom Palmer Eye Institute, University of Miami from December 2011 to September 2018. METHODS: Detailed ophthalmoscopic examination and FA were recommended to all new patients and performed on every patient who had parental consent. Ophthalmoscopic findings and FA images were graded for severity by two masked graders on a 3-point scale: 0 = no disease, 1 = vascular abnormalities without leakage, 2 = leakage or neovascularization, 3 = retinal detachment. Presence of known CNS disease was documented. Additional cases were obtained from a pediatric retina listserv for examples of phenotypic variation. MAIN OUTCOME MEASURES: Proportion of eyes noted to have disease on ophthalmoscopy compared with FA. Severity of retinal disease in those with and without known CNS disease. RESULTS: Retinal pathology was detected in 18/35 (51%) by indirect ophthalmoscopy and 26/35 (74%) by FA (p=0.048) in a predominantly pediatric population (median age = 9 months). Ten patients (29%) had known CNS disease at the time of the eye exam. A Wilcoxon ranked sums test indicated that the retinal severity scores for patients with CNS disease (median = 2) were significantly higher than the retinal severity scores for patients without CNS disease (median = 1), z = -2.12, p = 0.034. CONCLUSION: Retinal disease is present in the majority of patients with IP, and the ophthalmoscopic examination is less sensitive than FA for detection of disease. There may be a correlation between the severity of retinal and CNS disease.
Glonek T, Snogren T, Schmidt SY, Hearn SL, Isreb MA, Greiner JV. Phosphatic metabolism in dark- and light-adapted rat retinas. Exp Eye Res 2022;221:109141.Abstract
This study defines retinal phosphatic metabolites and their adjustment to illumination in rat retinas under conditions that preserve retinal function. Metabolic data are measured using high-performance liquid chromatography (HPLC) and 31P nuclear magnetic resonance (31P NMR) spectroscopy after 10 min of light exposure in vivo compared with retinas from dark-adapted rats. Multiple high-energy and low-energy phosphatic metabolites of intermediary metabolism were quantified. The concentration of the high-energy phosphate adenosine triphosphate (ATP) remained unchanged from dark- to light-adaptation. Under the same conditions the concentrations of the high-energy phosphates guanosine triphosphate (GTP) and creatine phosphate increased, whereas the inorganic phosphate decreased. Comparing dark-adapted controls with retinas light-adapted either in vitro or in vivo, the evidence is consistent with a light-dependent increase in GTP and a decrease in cyclic guanosine monophosphate. Although cyclic adenosine monophosphate (cAMP) levels were lower in retinas light-adapted in vivo than in the dark-adapted controls, this did not seem to be an effect of light, as cAMP levels decreased similarly after 10 min incubation in dark or light in parallel with recovery of ATP/adenosine diphosphate ratios. This study: (1) reports on retinal metabolic changes with adjustment in illumination, (2) provides baseline measurements of retinal phosphatic metabolites in whole retinas, and (3) reports on the validity of chromatographic and spectroscopic methods used for studying retinal metabolism establishing a high correlation among measurements made using HPLC and 31P NMR.
O'Hare M, Arboleda-Velasquez JF. Notch Signaling in Vascular Endothelial and Mural Cell Communications. Cold Spring Harb Perspect Med 2022;Abstract
The Notch signaling pathway is a highly versatile and evolutionarily conserved mechanism with an important role in cell fate determination. Notch signaling plays a vital role in vascular development, regulating several fundamental processes such as angiogenesis, arterial/venous differentiation, and mural cell investment. Aberrant Notch signaling can result in severe vascular phenotypes as observed in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and Alagille syndrome. It is known that vascular endothelial cells and mural cells interact to regulate vessel formation, cell maturation, and stability of the vascular network. Defective endothelial-mural cell interactions are a common phenotype in diseases characterized by impaired vascular integrity. Further refinement of the role of Notch signaling in the vascular junctions will be critical to attempts to modulate Notch in the context of human vascular disease. In this review, we aim to consolidate and summarize our current understanding of Notch signaling in the vascular endothelial and mural cells during development and in the adult vasculature.
Mei CY, Zhang Y, Pan L, Dong B, Chen X, Gao Q, Xu H, Xu W, Fang H, Liu S, McAlinden C, Paschalis EI, Wang Q, Yang M, Huang J, Yu A-Y. A One-Step Electrochemical Aptasensor Based on Signal Amplification of Metallo Nanoenzyme Particles for Vascular Endothelial Growth Factor. Front Bioeng Biotechnol 2022;10:850412.Abstract
In this study, a one-step electrochemical aptasensor was developed to detect the biomarker vascular endothelial growth factor (VEGF), an important protein in the pathogenesis of many retinal diseases, including age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, and retinal vein occlusion. The aptamer has a good affinity and can rapidly identify and capture VEGF based on its unique structure. We designed a VEGF aptasensor based on the aptamer recognition and complex metallo nanoenzyme particles as an electron exchange center and bridge between capture DNA and electrode. The aptamers maintained the hairpin structure to avoid nonspecific surface adsorption and expose the capture sequence outwards when the target was inexistent. Conversely, the aptamers opened the hairpin structure to release space to accomplish binding between VEGF and DNA, resulting in increased impedance. The performance of the electrochemical aptasensor is detected by electrochemical impedance spectroscopy (EIS). The limit of detection by EIS was as low as 8.2 pg ml-1, and the linear range was 10 pg ml-1-1 μg ml-1. The electrochemical aptasensor also showed high specificity and reproducibility.