DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for retinal vascular disorder — screening already-approved drugs against its 7-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleRetinal vascular disorder maps to a 7-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for retinal vascular disorder is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
RAS like family 12 (RASL12) — RASL12 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet gdpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3C5C · 1.85 Å · ligand GUANOSINE-5'-DIPHOSPHATE (GDP). Experimental structure, not a prediction.
What the evidence adds up to
In a mouse model of oxygen-induced ischemic retinopathy, calcitriol (1,25-dihydroxyvitamin D₃) reduced retinal neovascularisation in a dose-dependent manner. No deaths occurred, but treated mice showed increased serum calcium and a lack of weight gain. Ocular VEGF levels were not different between treated and control animals. In cultured retinal endothelial cells, calcitriol inhibited capillary morphogenesis at lower concentrations than those needed to block proliferation or migration. The same 2007 study notes that retinal angiogenesis is the basis of vision loss in several major blinding diseases.
A 2020 phenotypic screen of 2,100 known drugs identified eleven compounds that blocked interleukin-1β-induced hyperpermeability in cultured human retinal microvascular endothelial cells. Two of those, apigenin and ethaverine hydrochloride, reproducibly blocked hyperpermeability caused by multiple cytokines and stabilised three other types of primary vascular endothelial monolayers. The proposed mechanism involves blocking ARF6 activation and increasing VE-cadherin membrane localisation. Both compounds showed in vivo efficacy in an animal model of retinal permeability. The authors state these drugs would have potential therapeutic efficacy regardless of the underlying mechanism promoting vascular leak.
A 2011 case report describes a 71-year-old woman with a retinal arterial macroaneurysm causing preretinal and subretinal haemorrhage who received two intravitreal injections of bevacizumab within two months. Visual acuity and visual field were at normal levels at 39-month follow-up. The authors note that retinal macroaneurysm is a relatively rare condition and that anti-VEGF therapy may offer faster visual rehabilitation in selected symptomatic individuals.
A 2021 study in pigs tested whether subretinal saline injection before laser photocoagulation could protect the neuroretina from thermic damage while still inducing choroidal neovascularisation. From day 7, OCT showed subretinal density in all lesions, and fluorescein or OCT angiography confirmed CNV formation in 11 of 14 eyes in both the saline-pretreated and photocoagulation-only groups. In all saline-pretreated eyes the neuroretina was protected from immediate thermic damage. The largest lesions were seen within 14 days. A 2003 paper describes the Vldlr mutation mouse as a reliable genetic model of subretinal neovascularisation with choroidal anastomosis, noting that homozygosity for the mutation always segregated with retinal angiogenesis.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Calcitriol Is a Potent Inhibitor of Retinal Neovascularization
AbstractPURPOSE: Vitamin D compounds inhibit the growth of a variety of tumors in preclinical and clinical studies. Among the mechanisms suggested for this inhibition is antiangiogenesis. Retinal angiogenesis is the basis for vision loss in several major blinding diseases. The purpose of this study was to evaluate the antiangiogenic activity of calcitriol (1,25-dihydroxyvitamin D(3)) in vivo and its effect on retinal endothelial cell (EC) proliferation, migration, and capillary morphogenesis in vitro. METHODS: The mouse oxygen-induced ischemic retinopathy (OIR) model was used to assess the antiangiogenic activity of calcitriol. Ocular VEGF levels were determined by Western blot analysis of whole eye extracts from postnatal day (P) 15 mice during OIR. The effects of calcitriol on retinal EC proliferation, migration, and capillary morphogenesis were also assessed in vitro. RESULTS: Calcitriol-treated animals demonstrated a significant decrease in retinal neovascularization compared with control animals. This effect was dose dependent, and retinal neovascularization was significantly inhibited in calcitriol-treated mice. Although no deaths occurred, calcitriol administration was associated with increased serum calcium and a lack of increase in body weight in a dose-independent manner. The ocular level of VEGF was similar in control and calcitriol-treated animals. At a lower concentration of calcitriol, retinal EC capillary morphogenesis in solubilized basement membrane was inhibited without a significant inhibitory effect on EC proliferation and migration. The concentration of calcitriol required to inhibit retinal EC proliferation was significantly higher than that required to inhibit EC capillary morphogenesis. CONCLUSIONS: These data suggest calcitriol is a potent inhibitor of retinal neovascularization and may be of benefit in the treatment of a variety of eye diseases with a neovascular component.
MOUSE MODEL OF SUBRETINAL NEOVASCULARIZATION WITH CHOROIDAL ANASTOMOSIS
AbstractPURPOSE: To characterize the phenotype and report a reliable genetic model of retinal angiogenesis and subretinal neovascularization in the mouse. METHODS: The mouse phenotype was characterized using ophthalmoscopy, fundus photography, fluorescein angiography, electroretinography, histology, gene sequencing, and linkage analysis. RESULTS: Scattered pink-gray retinal lesions were found on ophthalmoscopy and were confirmed to be subretinal neovascularization on fluorescein angiography. On histologic examination, outer plexiform retinal neovascularization with growth into the subretinal space was found as early as postnatal Day 15. On genetic analysis, homozygosity of the Vldlr mutation always segregated with the retinal angiogenesis, whereas normal and heterozygous mice had no neovascularization. The histologic studies 15 to 18 days consistently showed new outer plexiform neovascular vessels drawn to the subretinal space by 20 days, and by 30 to 50 days, subretinal hemorrhages and choroidal anastomoses were common. Mice by 8 months had increased vascularity of the iris and ciliary body. CONCLUSIONS: The Vldlr mutation in the mouse provides a good model for retinal angiogenesis and subretinal neovascularization. Finding a strong association between retinal angiogenesis and a very low density lipid receptor mutation is new, and study of lipid receptor physiology may broaden the understanding of retinal angiogenesis.
Clinical ophthalmology · 2011 · 25 citations · open access
The use of bevacizumab in a multilevel retinal hemorrhage secondary to retinal macroaneurysm: a 39-month follow-up case report
AbstractPURPOSE: The evaluation of long-term visual outcome after the use of bevacizumab for the management of multilevel hemorrhage due to retinal arterial macroaneurysm (MA). CASE REPORT: A 71-year-old hypertensive female presented with sudden reduction of visual acuity in her left eye (OS). Fundoscopy revealed an arterial macroaneurysm with preretinal and subretinal hemorrhage in the eye. Due to significant macular involvement, the patient received two intravitreal injections of bevacizumab within 2 months. RESULTS: Significant visual and anatomical recovery was observed 2 months later, which was confirmed by fluorescein angiography. At the end of a follow-up period (39 months) visual acuity and visual field were at normal levels. CONCLUSION: Retinal MA is a relatively rare condition. Anti-vascular endothelial growth factor therapy appears a safe and effective treatment option for selected symptomatic individuals that may offer faster visual rehabilitation. Herein we report, for the first time, a 39-month follow-up of a retinal MA treated with anti-vascular endothelial growth factor therapy.
Apigenin and Ethaverine Hydrochloride Enhance Retinal Vascular Barrier In Vitro and In Vivo
AbstractPurpose: This study aims to develop an impedance-based drug screening platform that will help identify drugs that can enhance the vascular barrier function by stabilizing vascular endothelial cell junctions. Methods: Changes in permeability of cultured human retinal microvascular endothelial cells (HRMECs) monolayer were monitored in real-time with the xCELLigence RTCA system. Using this platform, we performed a primary screen of 2100 known drugs and confirmed hits using two additional secondary permeability assays: the transwell permeability assay and the XPerT assay. The cellular and molecular mechanisms of action and in vivo therapeutic efficacy were also assessed. Results: Eleven compounds blocked interleukin 1 beta (IL-1β) induced hyperpermeability in the primary screen. Two of 11 compounds, apigenin and ethaverine hydrochloride, reproducibly blocked multiple cytokines induced hyperpermeability. In addition to HRMEC monolayers, the two compounds stabilized three other types of primary vascular endothelial cell monolayers. Preliminary mechanistic studies suggest that the two compounds stabilize the endothelium by blocking ADP-ribosylation factor 6 (ARF6) activation, which results in enhanced VE-cadherin membrane localization. The two compounds showed in vivo efficacy in an animal model of retinal permeability. Conclusions: We developed an impedance-based cellular phenotypic drug screening platform that can identify drugs that enhance vascular barrier function. We found apigenin and ethaverine hydrochloride stabilize endothelial cell junctions and enhance the vascular barrier by blocking ARF6 activation and increasing VE-cadherin membrane localization. Translational Relevance: The drugs identified from the phenotypic screen would have potential therapeutic efficacy in retinal vascular diseases regardless of the underlying mechanisms that promote vascular leak.
Subretinal Saline Protects the Neuroretina From Thermic Damage During Laser Induction of Experimental Choroidal Neovascularization in Pigs
AbstractPurpose: The purpose of this study was to develop a porcine model for photocoagulation induced choroidal neovascularization (CNV) with high success rate and minimal thermic damage to the neuroretina. Methods: Experimental CNV was induced by laser photocoagulation in both eyes of 16 domestic pigs. In the left eyes, photocoagulation was preceded by subretinal injection of saline to protect the neuroretina from thermic damage, whereas the right eyes were treated with photocoagulation only. The development of the CNV after 3, 7, 14, 28, and 42 days was evaluated by optical coherence tomography (OCT) scanning, fluorescein angiography, and OCT angiography, and by histology after enucleation. Results: From day 7 after the photocoagulation, OCT showed subretinal density in all lesions of 14 alive animals, and either fluorescein or OCT angiography confirmed CNV formation in 11 of 14 of the eyes that had received photocoagulation alone and those in which photocoagulation had been preceded by subretinal injection of saline. In all cases pretreated with subretinal saline, the neuroretina was protected from immediate thermic damage. The formation of CNVs were confirmed by histology. For both groups, the largest lesions were observed within 14 days after photocoagulation. Conclusions: Injection of subretinal saline can protect the retina from thermic damage induced by retinal photocoagulation without reducing the success rate in producing experimental CNV. The effect of interventional studies aimed at reducing photocoagulation induced experimental CNV in pigs can be evaluated within 2 weeks after photocoagulation. Translational Relevance: This model provides a fundament to develop and evaluate novel treatment methods for neovascular retinal diseases.
South African Medical Journal · 2010 · 3 citations · open access
Association between clomiphene citrate and central retinal vein occlusion
AbstractCentral retinal vein occlusion (CRVO) is a common retinal vascular disorder associated with cardiovascular disorders and other related risk factors. A case of CRVO secondary to clomiphene citrate has been reported. We present a case that also illustrates the association between clomiphene citrate and CRVO, and hope that it will serve to increase awareness among physicians who use the drug.
DOAJ (DOAJ: Directory of Open Access Journals) · 2017 · 0 citations · open access
Advances in drug treatment of retinal vein occlusion
AbstractRetinalvein occlusion(RVO)is the most common retinal vascular disease. The main causes of visual impairment and blindness are macular edema and retinal neovascularization. Drug therapies are the effective and safe method in the treatment of RVO currently. The main drugs conclude corticosteroid drugs, anti-vascular endothelial growth factor drugs, thrombolytic drugs and traditional drugs. This article reviews the recent progress in RVO in order to provide some valuable references for clinical treatment.
Aflibercept Treatment and Regimes in Macular Edema Secondary to Central Retinal Vein Occlusion
AbstractCentral retinal vein occlusion (CRVO) is the most common vascular disease leading cause of vision loss after diabetic retinopathy (DR) and branch retinal vein occlusion (BRVO). The pathogenesis of CRVO involves a thrombus formation leading to increased retinal capillary pressure, increased vascular permeability, and possibly retinal neovascularization. Vision loss due to CRVO is commonly caused by macular edema. Multiple treatment modalities have been used to treat macular edema. Currently, the most common therapy modality used is intravitreal inhibition of vascular endothelial growth factor (VEGF). The three most widely used agents are aflibercept, bevacizumab, and ranibizumab. In addition, intraocular steroids can be used to treat macular edema. This review will briefly cover the treatment options and discuss in greater detail the efficacy and safety of aflibercept.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
