DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for foveal hypoplasia 1 — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleFoveal hypoplasia 1 maps to a 2-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 foveal hypoplasia 1 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
paired box 6 (PAX6) — PAX6 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6PAX · 2.5 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Foveal hypoplasia is defined by the absence of a foveal depression and the presence of the ganglion cell layer in the foveola. A 2014 case report describes a 16-year-old with mild to moderate visual impairment since early childhood, in whom lack of foveal depression was noted on examination and optical coherence tomography, and absence of the foveal avascular zone was demonstrated on fluorescein angiography. A 2019 case reports a 9-year-old boy with moderately decreased vision in the left eye, absent macular reflection, no foveal pit on optical coherence tomography, and absence of the foveal avascular zone on angiography. A 2020 case report describes a 25-year-old woman with foveal hypoplasia who had best-corrected visual acuity of 20/15 in both eyes; spectral domain optical coherence tomography showed absence of the foveal pit with normal inner retinal morphology, and optical coherence tomography angiography confirmed a decreased foveal avascular zone but normal perfusion to the inner retinal plexuses. A 2022 review notes that foveal hypoplasia can present with normal or variably decreased visual acuity and is associated with albinism, aniridia, nanophthalmos, prematurity, and fovea plana.
A 2018 study used aniridia as a disease model to investigate foveal hypoplasia at the cellular and molecular levels. In 33 aniridia subjects from British Columbia, foveal hypoplasia was seen in 80% of those in whom imaging was possible. Best corrected visual acuities in the cohort ranged from normal vision to no light perception. Molecular genetic defects involving PAX6 were identified in 30 participants, including 4 novel PAX6 mutations and 4 novel chromosome 11p deletions inclusive of PAX6 or its regulatory region. As a proof-of-principle, the study employed spliceosome-mediated RNA trans-splicing to rescue Pax6 defects in homozygous-mutant mouse embryonic fibroblasts and then in vivo in a naturally occurring Pax6 mouse model, showing that Pax6 expression could be rescued in vitro and in vivo. The study also tested the green anole lizard as a foveated model: bioinformatic analysis found that 85% of human candidate foveal hypoplasia genes had an orthologous gene or DNA sequence in the anole, and embryonic foveal development in green anoles was shown to resemble human foveal development during infancy.
No treatment is yet available for vision loss resulting from an underdeveloped fovea. The 2018 study notes that little is known about foveal pathologies and development at the cellular and molecular levels. The SMaRT method for Pax6 rescue was demonstrated only in mouse models, not in humans. What is still missing is a human trial of any molecular therapy, funding for such a trial, and a clear stratification of patients by genetic defect or severity of foveal hypoplasia to determine who might benefit.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Optometry and Vision Science · 2014 · 13 citations
Isolated Foveal Hypoplasia
AbstractPURPOSE: To describe the clinical presentation and imaging findings of a patient with isolated foveal hypoplasia. CASE REPORT: A 16-year-old teenager presented to our clinic with mild to moderate visual impairment since early childhood. Lack of foveal depression was noted on both clinical examination and optical coherence tomography, and absence of the foveal avascular zone was demonstrated on fluorescein angiography. His ocular examination was otherwise unremarkable. CONCLUSIONS: Isolated foveal hypoplasia should be considered in the differential diagnosis of early-onset bilateral visual impairment, especially when the foveal reflexes seem absent.
American Journal of Case Reports · 2019 · 3 citations · open access
Fovea Plana in a 9-Year-Old Boy Presenting with Decreased Vision in the Left Eye
AbstractBACKGROUND Foveal hypoplasia (FH) is a congenital disorder, generally associated with other conditions. CASE REPORT A 9-year-old boy presented with moderately decreased vision in the left eye. Fundus examination showed an absence of macular reflection and no foveal pit was seen on optical coherence tomography. Fluorescein angiography demonstrated the absence of a foveal avascular zone. CONCLUSIONS This is a rare case of a unilateral fovea plana associated with a visual impairment.
Case Report: Optical Coherence Tomography Angiography of Idiopathic Foveal Hypoplasia and Its Correlation With Visual Acuity
AbstractSIGNIFICANCE: Foveal hypoplasia is described clinically by the absence of a foveal pit and subsequent reduction in visual acuity. Optical coherence tomography angiography provides precise segmentation of the retinal vascular supply demonstrating the vascular perfusion in affected patients. Preservation of perfusion is linked to visual acuity and function. PURPOSE: This case report describes a patient with foveal hypoplasia and preservation of visual acuity with preserved retinal capillary density of the superficial and deep capillary plexuses on optical coherence tomography angiography. In addition, the diagnostic findings of foveal hypoplasia as seen on optical coherence tomography angiography will be described. CASE REPORT: A 25-year-old Caucasian female with history of foveal hypoplasia presented to the clinic for evaluation. She had no other visual, ocular, or systemic complaints. Her ocular history included Duane syndrome, accommodative insufficiency, and traumatic brain injury. Her medical history included cardiac ablation secondary to supraventricular tachycardia, gall bladder removal, maxillary sinus cyst, and a history of migraines. Best-corrected visual acuity was 20/15 in the right and left eyes. Funduscopic examination was unremarkable. Spectral domain optical coherence tomography revealed absence of the anatomical foveal pit with normal inner retinal morphology. Optical coherence tomography angiography confirmed a decreased foveal avascular zone; however, a vascular density analysis showed normal perfusion to the inner retinal plexuses. CONCLUSIONS: Optical coherence tomography angiography is a rapid, noninvasive imaging modality that provides excellent insight into the microvasculature supply to the retina and choroid. As such, it allows for an in-depth analysis into the pathophysiology behind certain conditions such as foveal hypoplasia.
Therapeutic Advances in Ophthalmology · 2022 · 0 citations · open access
Clinical spectrum of blunted foveal contour
AbstractFoveal hypoplasia is the absence of a foveal depression and the presence of the ganglion cell layer in the foveola. A spectrum of clinical characteristics, including normal or variably decreased visual acuity, has been described in patients with blunted foveal contours. Multiple systemic and ophthalmologic conditions including albinism, aniridia, nanophthalmos, prematurity, and fovea plana have been associated with this anomaly. This article illustrates select clinical conditions characterized by a blunted foveal contour. Given the heterogeneity of findings, a thorough medical history and detailed physical and ocular examinations are usually sufficient for the clinician to make the correct diagnosis.
cIRcle (University of British Columbia) · 2018 · 0 citations · open access
Genetic insights into the role of PAX6 in ocular development
AbstractThe fovea is a small retinal indentation packed with specialized cone photoreceptors. Despite its key-role in central vision, little is known about foveal pathologies and development at the cellular and molecular levels. Therefore, no treatment is yet available for vision loss resulting from underdeveloped-fovea (foveal hypoplasia (FH)). First, I used aniridia as a disease model to better understand FH at the cellular and molecular levels. Thirty-three aniridia subjects from British Columbia underwent a thorough ophthalmic examination with in-vivo imaging of foveal structure. Molecular investigations include sequencing of PAX6, candidate genes, in addition to 11p chromosomal analysis. In those in whom imaging was possible, FH was seen in the majority (80%) of cases. Best corrected visual acuities in the cohort ranged from normal vision to no light-perception. Molecular genetic defects involving PAX6 were identified in 30 participants, including 4 novel PAX6 mutations and 4 novel chromosome 11p deletions inclusive of PAX6 or its regulatory region. Then as a proof-of-principle, we employed the SMaRT (spliceosome-mediated RNA trans-splicing) method to rescue Pax6 defects in homozygous-mutant mouse embryonic-fibroblasts and then in-vivo in a naturally occurring Pax6 mouse model. We showed that by using SMaRT technology we were able to rescue Pax6 expression in-vitro and in-vivo, paving the way for potential future therapies for FH. Finally, we tested the feasibility of using Anolis carolinensis (green anole lizard) as a novel foveated model. With its complete published genome, bioinformatic analysis revealed that 85% of human candidate FH genes had an orthologous gene or DNA sequence in the anole. Eyes were collected at various stages of prehatching development for histological analysis, immunofluorescence, and apoptosis analysis. We demonstrated that embryonic foveal development in green anoles resembles human foveal development during infancy. Additionally, at embryonic stage (ES) 14 Pax6 was localized across the entire retina. However, at ES17 Pax6 expression in the ganglion cells of the central retina was markedly reduced. These findings provide the first insight into foveal morphogenesis in the green anole and suggest that it could be an ideal model for perturbing the molecular signals driving foveal development, thus informing on human foveal development and disease.
Kerala Journal of Ophthalmology · 2024 · 0 citations · open access
Isolated foveal hypoplasia: A case series
AbstractFoveal hypoplasia is a well-known condition characterized by an absent or abnormal foveomacular reflex. It may occur in isolation or in association with aniridia, albinism, achromatopsia, microphthalmos, and other anterior segment anomalies. The clinical diagnosis might often be missed due to the subtle nature of findings. We describe five cases of two families with isolated foveal hypoplasia. The presence of nystagmus and unexplained poor vision in children without features of retinal dystrophies should raise a suspicion of isolated foveal hypoplasia. Detailed and careful fundus examination, especially the foveal area, helps in diagnosing the same.
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.
