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The Largest Glaucoma Genome Study Yet Found 29 New Genetic Clues — Could Existing Drugs Target Some of Them? · Glaucoma, Vision & Longevity: Supplements & Science

• 0:00
  SPEAKER_00: The largest glaucoma genome study yet found 29 new genetic clues.
• 0:04
  SPEAKER_00: Could existing drugs target some of them?
• 0:07
  SPEAKER_00: The short answer is possibly, but the study did not identify a ready-made glaucoma drug.
• 0:12
  SPEAKER_00: It found genetic associations that point towards several plausible disease mechanisms, including extracellular matrix remodeling, aqueous fluid outflow, cellular stress responses, and retinal ganglion cell survival.
• 0:25
  SPEAKER_00: Among the four highlighted drug targets, the mammalian target of rapamycin pathway has the strongest combination of genetic, experimental, and drug delivery evidence.
• 0:36
  SPEAKER_00: Even there, the right direction and amount of treatment remain uncertain.
• 0:40
  SPEAKER_00: A critical distinction: a gene associated with glaucoma is not automatically a treatment target.
• 0:46
  SPEAKER_00: The genetic finding may not reveal what the variant does, which I cell it affects, or whether a drug should increase or decrease the gene's activity.
• 0:55
  SPEAKER_00: The paper itself cautions that, for most of these associations, pharmacological direction cannot yet be predicted.
• 1:03
  SPEAKER_00: This article distinguishes established evidence, what the studies directly report from strong inference and informed speculation about possible treatments.
• 1:11
  SPEAKER_00: What the study actually found.
• 1:14
  SPEAKER_00: The Communications Biology paper was published online on September 23, 2026.
• 1:20
  SPEAKER_00: Its early access version is peer-reviewed, but still described by the publisher as an article in press that may receive further edits.
• 1:28
  SPEAKER_00: It is a genetic association study, not a clinical trial, cohorts and ancestry.
• 1:33
  SPEAKER_00: For the full table, please open this article on VisualFieldtest.com.
• 1:38
  SPEAKER_00: The discovery and replication sequencing analyses were restricted to participants of European ancestry.
• 1:44
  SPEAKER_00: The paper says 464,778 European ancestry participants made up about 95% of its UK Biobank whole genome sequencing resource.
• 1:54
  SPEAKER_00: The All of Us Replication Sample was also European ancestry.
• 1:58
  SPEAKER_00: FinGen represents a Finnish population, while the Million Veteran Program is ancestrally diverse overall, but the study's cited open angle glaucoma analysis used its European ancestry results.
• 2:09
  SPEAKER_00: Thus, the large headline sample does not mean that the principal discovery and replication findings were tested across equally large diverse ancestry groups.
• 2:19
  SPEAKER_00: The authors also report a preliminary UK Biobank panancestry analysis that found 15 additional significant variants, 11 rare and 4 common.
• 2:28
  SPEAKER_00: They had external replication evidence for only one of those, a common variant near ADGRB2.
• 2:35
  SPEAKER_00: The authors note that many signals were not present or testable in current external data sets.
• 2:41
  SPEAKER_00: Important caveat: the replication phenotype was broader than the discovery phenotype.
• 2:45
  SPEAKER_00: In UK Biobank, cases were identified from self-reported glaucoma and medical record codes, with secondary forms excluded.
• 2:53
  SPEAKER_00: In all of us, the researchers used medical record codes for glaucoma because that definition had more cases and greater statistical power than the smaller primary open-angle glaucoma-specific definition.
• 3:06
  SPEAKER_00: This means the replication check was not a perfect match to the primary open-angle glaucoma discovery phenotype.
• 3:13
  SPEAKER_00: FinGEN used a primary open-angle glaucoma endpoint.
• 3:16
  SPEAKER_00: The Million Veteran Program used an open-angle glaucoma phenotype.
• 3:21
  SPEAKER_00: That does not invalidate the replication evidence, but it makes the word replication less straightforward than it may sound.
• 3:29
  SPEAKER_00: A signal that appears in a broader glaucoma group is supportive.
• 3:32
  SPEAKER_00: It is not the same as reproducing the exact association in an independently diagnosed primary open angle glaucoma cohort.
• 3:40
  SPEAKER_00: Sequencing, variant thresholds, and statistical significance.
• 3:44
  SPEAKER_00: The UK Biobank genomes were sequenced on an Illumina NovaSeq 6000 platform at an average depth of about 32.5 fold.
• 3:53
  SPEAKER_00: The researchers used graph typer called single nucleotide variants and insertions or deletions, applied quality filters, and used RIGNI, a method designed to account for population structure and relatedness.
• 4:06
  SPEAKER_00: Single variant analyses included variants with a minor allele count of at least five and tested variants within genes, including a one kilobase margin, intergenic variants were excluded.
• 4:17
  SPEAKER_00: The paper categorizes variants with an effect allele frequency below 1% as rare.
• 4:22
  SPEAKER_00: For single variant tests, genome-wide significance was P5 tonism.
• 4:28
  SPEAKER_00: For gene-based rare variant tests, the threshold was P2.5 toncets, based on correction for roughly 20,000 genes.
• 4:37
  SPEAKER_00: The gene-based analysis used loss of function variants and, in another test, combined loss of function, missense, and nearby regulatory variants.
• 4:47
  SPEAKER_00: For external checks, the authors looked up significant variants and genes in all of us, FinGen, and the Million Veteran Program.
• 4:55
  SPEAKER_00: If an exact rare variant was not available, they sometimes counted a significant variant elsewhere in the same gene region as support.
• 5:03
  SPEAKER_00: The methods do not describe one uniform, strict replication threshold applied to every variant and gene.
• 5:09
  SPEAKER_00: The paper's replicated or supported label therefore covers different kinds and strengths of evidence.
• 5:15
  SPEAKER_00: The 29 new clues were not 29 new genes.
• 5:19
  SPEAKER_00: The study reports 29 novel genome-wide significant rare variant associations.
• 5:25
  SPEAKER_00: That is not the same as finding 29 new glaucoma genes.
• 5:28
  SPEAKER_00: The complete table contains 36 genome-wide significant rare variants, including established variants in MIOC and OPTN.
• 5:36
  SPEAKER_00: A gene may contain a rare association without the study proving that the gene itself is the causal effector.
• 5:42
  SPEAKER_00: Among the highlighted novel rare variants were, for the full table, please open this article on VisualFieldTest.com.
• 5:50
  SPEAKER_00: The paper also confirmed known rare variant associations in MIOC and OPTN.
• 5:55
  SPEAKER_00: These confirmations help show that the analysis can recover established biology.
• 5:59
  SPEAKER_00: They are not new treatment findings.
• 6:01
  SPEAKER_00: Gene-based testing identified six significant genes, DDR2, MIOC, LTBP2, MTOR, ANGPTL7, and FKBP9.
• 6:09
  SPEAKER_00: The paper described new gene-based associations for DDR2, LTBP2, MTOR, MGTL7, and FKBP9, while MIOC is already an established glaucoma gene.
• 6:19
  SPEAKER_00: The gene-based associations for DDR2 and LTBP2 came from loss of function variants, MTOR, ANGPTL7, and FKBP9 were identified using broader variant sets.
• 6:29
  SPEAKER_00: The paper also reported common variant associations in 22 genes not previously reported as gene-level primary open-angle glaucoma associations.
• 6:38
  SPEAKER_00: MAPT appears in a common variant signal near the Canzel MAPT region.
• 6:43
  SPEAKER_00: LIN, by contrast, is highlighted in connection with a rare single variant association.
• 6:48
  SPEAKER_00: These are different kinds of evidence and should not be treated as equally precise gene identifications.
• 6:54
  SPEAKER_00: What biology do the new signals point toward?
• 6:56
  SPEAKER_00: The researchers examined gene expression datasets from ocular tissues and cell types.
• 7:02
  SPEAKER_00: They found evidence that many associated genes are expressed in trabecular meshwork cells, Schlem's canal, retinal ganglion cells, retinal support cells, or optic nerve and posterior eye tissues.
• 7:15
  SPEAKER_00: That supports biological plausibility, but expression does not prove that a gene causes glaucoma.
• 7:21
  SPEAKER_00: The expression analyses were based on existing datasets, not new experiments in diseased human eyes.
• 7:26
  SPEAKER_00: The most plausible biological interpretations aqueous outflow and intraocular pressure, LTBP2, ANGTL7, PRX1, and TNS3 are plausible candidates for effects on connective tissue, cell attachment, extracellular matrix, or outflow pathway remodeling.
• 7:44
  SPEAKER_00: The trabecular meshwork is a major site of resistance to aqueous fluid drainage, and Schlem's canal helps carry that fluid out of the eye.
• 7:52
  SPEAKER_00: Retinal ganglion cell resilience and axon health, MNOR, PRC2C, DEF1AKNMT, and some of the other associated genes are plausible participants in cellular stress responses, protein production, or the survival of retinal neurons and their axons.
• 8:09
  SPEAKER_00: Several associated genes were detectable in retinal ganglion cells or retinal support cells.
• 8:14
  SPEAKER_00: Metabolism and vascular biology.
• 8:17
  SPEAKER_00: FMO3 is primarily a liver enzyme involved in metabolism of trimethylamine.
• 8:22
  SPEAKER_00: The paper proposes a possible systemic route involving trimethylamine NOxide and vascular function, but this is not evidence that the glaucoma-associated variant acts in the eye.
• 8:32
  SPEAKER_00: Glial and inflammatory biology.
• 8:34
  SPEAKER_00: The paper found expression of genes including Lin, mTOR, and PRRC2C in retinal mular glia or astrocytes.
• 8:42
  SPEAKER_00: These cells support retinal neurons and participate in stress responses.
• 8:46
  SPEAKER_00: Expression alone cannot show whether their activity is protective or harmful in glaucoma.
• 8:52
  SPEAKER_00: Functional predictions are leads, not measurements.
• 8:56
  SPEAKER_00: The authors used Alpha Genome, a computational model that predicts effects on features such as gene regulation, chromatin accessibility, and splicing.
• 9:05
  SPEAKER_00: Among 29 novel rare variants analyzed, 12 had at least one predicted effect above the paper's threshold in an eye-related tissue or cell type.
• 9:14
  SPEAKER_00: Predictions for metal 13 and DNM3 included trabecular meshwork effects.
• 9:19
  SPEAKER_00: The FMO3 variant had a predicted splice-related effect.
• 9:23
  SPEAKER_00: The authors state that they did not experimentally validate these predictions.
• 9:28
  SPEAKER_00: A model-predicted increase or decrease in an assay track also does not, by itself, establish that the gene's activity increased or decreased in the relevant living eye cell.
• 9:38
  SPEAKER_00: Four drug-highlighted genes.
• 9:40
  SPEAKER_00: What might and might not be actionable?
• 9:43
  SPEAKER_00: The paper used the Open Targets platform to identify genes with existing drug annotations.
• 9:48
  SPEAKER_00: Its four highlighted targets were mTOR, DDR2, LIN, and MAPT.
• 9:53
  SPEAKER_00: That is a useful starting point for drug discovery, but drug-targetable does not mean a drug is approved for glaucoma, reaches the relevant eye tissue, or acts in the right direction.
• 10:03
  SPEAKER_00: MTOR, strongest convergence, but a double-edged target.
• 10:07
  SPEAKER_00: What the genetics says.
• 10:09
  SPEAKER_00: mTOR was significant in gene-based rare variant analysis.
• 10:12
  SPEAKER_00: The burden test combines several kinds of variants, so it does not identify one simple increase or decrease in mTOR activity.
• 10:20
  SPEAKER_00: The paper also cites an independent large exome analysis in which rare variant carriers in mTOR had lower glaucoma risk, with an estimated odds ratio of 0.87.
• 10:31
  SPEAKER_00: That is suggestive, not proof that reducing mTOR activity is protective.
• 10:35
  SPEAKER_00: The variants were functionally mixed, and the study did not directly measure mTOR activity in the eye.
• 10:42
  SPEAKER_00: What drugs exist?
• 10:43
  SPEAKER_00: Approved medicines that inhibit the mTOR pathway include serrolimis, Everolamus, and Temcerolamis, used for conditions other than glaucoma.
• 10:52
  SPEAKER_00: Additional mTOR or combined pathway inhibitors have been studied in cancer and other diseases.
• 10:58
  SPEAKER_00: Torin-2 is experimental, not an approved glaucoma medicine.
• 11:02
  SPEAKER_00: The genetics paper's drug table also lists a range of investigational mTOR compounds.
• 11:07
  SPEAKER_00: Does a drug reach the eye?
• 11:08
  SPEAKER_00: Oral treatment gives systemic exposure, but does not establish a useful or safe concentration in the retina or optic nerve.
• 11:16
  SPEAKER_00: Local delivery is more plausible for an eye-limited treatment.
• 11:20
  SPEAKER_00: Intravetrial serolamus has been studied in people with posterior eye inflammation, and ocular studies describe prolonged drug presence in eye tissues after local injection.
• 11:30
  SPEAKER_00: Those findings show that ocular delivery is feasible.
• 11:34
  SPEAKER_00: They do not show that serroleamus prevents glaucoma.
• 11:37
  SPEAKER_00: There is unusually relevant experimental evidence.
• 11:41
  SPEAKER_00: A 2026 study reported that impaired autophagy and mitochondrial turnover contributed to retinal ganglion cell injury in glaucoma models.
• 11:50
  SPEAKER_00: Intravitrial torin II, which inhibits mTOR and can stimulate autophagy, improved retinal ganglion cell and axon outcomes in mouse models, and protected retinal tissue in an ex-vivo human retinal explant experiment.
• 12:04
  SPEAKER_00: In the myosillin-related mouse model, some benefit may have reflected reduced eye pressure as well as neuronal protection.
• 12:11
  SPEAKER_00: This is promising preclinical evidence, not evidence of patient benefit.
• 12:16
  SPEAKER_00: The reported mouse injection concentration was 1 millimolar, which cannot be converted directly into a safe or effective human dose.
• 12:25
  SPEAKER_00: The central problem: mTOR has different effects in different cell types and through different protein complexes.
• 12:32
  SPEAKER_00: Inhibiting one part of the pathway may encourage autophagy, while excessive or poorly timed inhibition could interfere with protein synthesis, cell maintenance, or neuronal survival.
• 12:43
  SPEAKER_00: Systemic mTOR inhibitors also carry important risks, including immune suppression and other adverse effects.
• 12:50
  SPEAKER_00: Strong inference a carefully dosed local treatment that restores impaired autophagy may be more promising than broad, long-term systemic mTOR suppression.
• 12:59
  SPEAKER_00: The genetic study does not yet specify which drug, dose, eye compartment, or treatment schedule would accomplish that safely.
• 13:07
  SPEAKER_00: DDR2.
• 13:08
  SPEAKER_00: Genetics may argue against the available inhibitor, what the genetics says.
• 13:13
  SPEAKER_00: The DDR2 gene level signal was driven by rare loss of function variants.
• 13:17
  SPEAKER_00: The paper reports markedly elevated glaucoma risk among carriers, with an odds ratio of 6.94 and replication support in all of us.
• 13:26
  SPEAKER_00: That pattern suggests that normal DDR2 function may be protective, although a small number of rare variant carriers and possible variant-specific effects make the estimate uncertain.
• 13:37
  SPEAKER_00: What the protein does.
• 13:39
  SPEAKER_00: DDR2 is a collagen-activated receptor, tyrosine kinase.
• 13:44
  SPEAKER_00: The paper places it in trabecular meshwork fibroblast-like cells and posterior eye cell types and discusses its links to collagen signaling, extracellular matrix remodeling, and vascular development.
• 13:55
  SPEAKER_00: These observations make an outflow pathway or tissue maintenance mechanism plausible.
• 14:00
  SPEAKER_00: What drug exists?
• 14:02
  SPEAKER_00: Rigoraphanib is an approved oral cancer medicine that inhibits multiple kinases, including DDR2, among its targets.
• 14:10
  SPEAKER_00: It is not a selective DDR-2 medicine.
• 14:12
  SPEAKER_00: It has also been investigated as an eyedrop treatment for neovascular age-related macular degeneration, showing that ocular formulations have been explored.
• 14:21
  SPEAKER_00: That is not proof of useful delivery to glaucoma-relevant tissues.
• 14:25
  SPEAKER_00: Directionality is the warning.
• 14:28
  SPEAKER_00: If reduced DDR2 function raises glaucoma risk, then inhibiting DDR2 with rigoraphanib could theoretically push in the wrong direction.
• 14:36
  SPEAKER_00: The study did not show that DDR2 activation treats glaucoma, and no validated DDR2 activating glaucoma drug is established.
• 14:44
  SPEAKER_00: Strong inference, DDR2 is an interesting biological target, but existing DDR2 inhibiting drugs should not be assumed to be promising glaucoma therapies.
• 14:55
  SPEAKER_00: Lynn, a plausible cell signaling target without a usable direction.
• 14:59
  SPEAKER_00: The study reports a rare variant within the LIN region, but the association does not establish whether the variant increases or decreases LIN activity or whether Lyan itself is the causal gene.
• 15:11
  SPEAKER_00: Lin is expressed in mouse schlems canal endothelial cells and in retinal support cells in the datasets discussed by the authors.
• 15:18
  SPEAKER_00: That makes it biologically relevant to consider, but not yet a validated target.
• 15:24
  SPEAKER_00: Existing medicines such as disatinib and bosutinib inhibit broad families of kinases that include lin-related activity.
• 15:31
  SPEAKER_00: They were developed for blood cancers, not glaucoma.
• 15:35
  SPEAKER_00: The paper also lists investigational kinase drugs.
• 15:38
  SPEAKER_00: Broad systemic inhibition is not an attractive long-term glaucoma strategy without evidence that it is beneficial in the right ocular cell type.
• 15:47
  SPEAKER_00: The study does not establish whether inhibition or activation would be preferable, and it provides no glaucoma-specific ocular drug concentration target.
• 15:57
  SPEAKER_00: Informed speculation, if LIN proves important in a particular ocular immune or support cell population, local and highly selective delivery might eventually be considered.
• 16:08
  SPEAKER_00: At present, LIN is a biological lead, not a reason to use an existing systemic kinase inhibitor for glaucoma.
• 16:15
  SPEAKER_00: MAPT, an intriguing neurodegeneration link, not proof of Tau-driven glaucoma.
• 16:20
  SPEAKER_00: MAPT encodes Tau, a protein best known for its role in Alzheimer's disease and other Tau-related neurodegenerative conditions.
• 16:27
  SPEAKER_00: In this study, MAPT was highlighted from a common variant association near the Canz L1 MAPT region.
• 16:34
  SPEAKER_00: That does not prove that MAPT is the causal gene.
• 16:37
  SPEAKER_00: The association is non-coding and sits in a region containing more than one plausible gene.
• 16:43
  SPEAKER_00: The paper does not show that the variant changes Tau abundance, Tau aggregation, or Tau activity in retinal ganglion cells.
• 16:50
  SPEAKER_00: Tau-directed antibodies and other Tau-related medicines are under investigation for neurological conditions.
• 16:57
  SPEAKER_00: The paper lists several investigational Tau agents.
• 17:00
  SPEAKER_00: There is no approved Tau-directed glaucoma treatment established by this study.
• 17:05
  SPEAKER_00: Antibodies given systemically face the additional question of whether enough drug reaches the retina and optic nerve.
• 17:12
  SPEAKER_00: Intravitrial delivery is conceivable, but the study offers no glaucoma-specific evidence that it would achieve target engagement or improve vision.
• 17:21
  SPEAKER_00: Does this strengthen the Alzheimer's glaucoma hypothesis?
• 17:25
  SPEAKER_00: A little, but not much.
• 17:27
  SPEAKER_00: The MAPT Region Association adds a genetic clue compatible with overlapping neurodegenerative biology.
• 17:33
  SPEAKER_00: Because the causal gene and functional direction are unresolved, it does not demonstrate that glaucoma is a tau apathy or that anti-Tau treatment would help patients.
• 17:44
  SPEAKER_00: Informed speculation, Tau could matter in a subset of disease processes, but this finding is better treated as a prompt for experiments than as a treatment rationale.
• 17:54
  SPEAKER_00: The mTOR, autophagy and mitochondrial connection.
• 17:58
  SPEAKER_00: A promising feature of the mTOR result is that it sits beside an independent body of experimental work on cellular cleanup and energy balance.
• 18:06
  SPEAKER_00: The 2026 TORIN-2 study reported impaired autophagy, the process cells use to break down and recycle damaged material, and abnormal mitochondrial accumulation in glaucoma models.
• 18:18
  SPEAKER_00: Its results suggest that restoring this process can protect retinal ganglion cells and their axons.
• 18:25
  SPEAKER_00: This provides mechanistic convergence with the MTOR association, although the human genetics study and the Torin-2 experiments do not prove the same causal chain.
• 18:35
  SPEAKER_00: Separate preclinical research on nicotinamide and nicotinamide-adinine dinucleotide metabolism has also reported retinal ganglion cell protection in glaucoma models.
• 18:45
  SPEAKER_00: Nicotinamide supplies material for producing nicotinamide-adenine dinucleotide, a molecule central to cellular energy and redox balance.
• 18:54
  SPEAKER_00: This supports the broader idea that retinal ganglion cell aging, metabolic stress, and mitochondrial health matter in glaucoma.
• 19:02
  SPEAKER_00: It does not specifically validate mTOR as the driver of those changes.
• 19:06
  SPEAKER_00: Taken together, established evidence, the genetics paper found an MTOR gene-level association.
• 19:13
  SPEAKER_00: Independent laboratory studies report autophagy and mitochondrial abnormalities in glaucoma models with protective effects from torin-2 under experimental conditions.
• 19:23
  SPEAKER_00: Strong inference, mTOR-linked control of autophagy and stress responses is a credible glaucoma research pathway.
• 19:31
  SPEAKER_00: Informed speculation, a local cell-selective treatment that restores an appropriate level of autophagy could protect retinal ganglion cells without harmful effects elsewhere in the eye.
• 19:42
  SPEAKER_00: No such treatment has yet been validated for glaucoma patients.
• 19:46
  SPEAKER_00: Comparison with the Artificial Intelligence and Optical Coherence Tomography Genetics Study.
• 19:52
  SPEAKER_00: A separate 2026 study used machine learning-derived optical coherence tomography measures of glaucoma-related retinal damage and genetic data from 47,908 UK Biobank participants.
• 20:05
  SPEAKER_00: It reported 21 novel glaucoma-related loci and prioritized 11 putative causal genes using gene-based analysis, genetic collocalization, Mendelian randomization, and cell type analysis.
• 20:18
  SPEAKER_00: Its proposed mechanisms included WNT-related outflow changes and retinal ganglion cell vulnerability.
• 20:25
  SPEAKER_00: The two studies do not share an obvious overlap among their explicitly prioritized gene lists.
• 20:30
  SPEAKER_00: The optical coherence tomography study highlighted genes including RSPO2, EIF3E, NPLOF 41I2, and SLC25A12.
• 20:39
  SPEAKER_00: These are not the central rare variant or drug target findings of the whole genome sequencing paper.
• 20:45
  SPEAKER_00: There is, however, pathway level convergence.
• 20:48
  SPEAKER_00: The optical coherence tomography study linked RSP2 to WINT signaling and connective tissue cells in the trabecular meshwork, ciliary body, and optic nerve head.
• 20:57
  SPEAKER_00: The whole genome sequencing study independently points to outflow pathway and matrix biology through genes such as DDR2, LTBP2, ANGPTL7, and TNS3.
• 21:09
  SPEAKER_00: Both studies implicate cells that support retinal ganglion cells and the optic nerve, rather than pointing only to eye pressure.
• 21:16
  SPEAKER_00: The optical coherence tomography study found cell type signals involving retinal ganglion cells, fibroblasts, and astrocytes.
• 21:23
  SPEAKER_00: The whole genome sequencing study found associated gene expression in retinal ganglion cells, glia, and optic nerve or posterior eye cells.
• 21:32
  SPEAKER_00: That is, biological convergence, not replication of the same genes.
• 21:37
  SPEAKER_00: The studies use different phenotypes and methods, and their results should not be treated as interchangeable.
• 21:43
  SPEAKER_00: Which opportunities look most actionable?
• 21:46
  SPEAKER_00: For the full table, please open this article on VisualFieldTest.com.
• 21:50
  SPEAKER_00: The ranking is not a clinical recommendation.
• 21:53
  SPEAKER_00: It balances the strength of the genetic signal with biological plausibility and the availability of compounds.
• 22:00
  SPEAKER_00: In particular, the existence of a drug is not an advantage if it acts in the wrong direction.
• 22:05
  SPEAKER_00: That is the concern for DDR2 inhibitors and, in a different way, for broad mTOR suppression.
• 22:12
  SPEAKER_00: How likely are the discoveries to produce treatment?
• 22:15
  SPEAKER_00: The following are informed estimates, not probabilities calculated by the study.
• 22:20
  SPEAKER_00: They refer to the period beginning with the paper's September 2026 publication.
• 22:25
  SPEAKER_00: At least one newly implicated gene is genuinely causal in glaucoma, roughly 60 to 80%.
• 22:31
  SPEAKER_00: The number of rare signals, the recovery of myoc and OPTN, and support for some findings in independent datasets make it plausible that at least one new signal reflects true biology.
• 22:43
  SPEAKER_00: The estimate is lower for any one particular new gene because many variants remain functionally unexplained.
• 22:50
  SPEAKER_00: At least one becomes a validated therapeutic target, roughly 25 to 40%.
• 22:55
  SPEAKER_00: A genetic association must still be assigned to the causal gene, its effect must be understood, and manipulating it must improve disease in relevant models.
• 23:04
  SPEAKER_00: An existing drug can be meaningfully repurposed, roughly 10 to 20%.
• 23:09
  SPEAKER_00: Local serrolimus experience and the availability of kinase inhibitors make repurposing technically conceivable, but they do not establish a safe, useful glaucoma dose or even the correct pharmacological direction.
• 23:22
  SPEAKER_00: One of these pathways enters a glaucoma clinical trial within five years, roughly 25 to 40%.
• 23:29
  SPEAKER_00: MTOR-linked autophagy is the most likely pathway to move first because it has relevant preclinical glaucoma evidence and existing ocular delivery experience with related medicines.
• 23:40
  SPEAKER_00: A trial would still require stronger safety, dose, and mechanism data.
• 23:46
  SPEAKER_00: The study itself does not establish that one of the four targets is already being clinically tested as a glaucoma treatment.
• 23:53
  SPEAKER_00: The human ocular delivery evidence for Serolamus comes from other eye diseases, and rigoraphanib eyedrop studies were aimed at macular degeneration, not glaucoma.
• 24:03
  SPEAKER_00: Conclusion.
• 24:04
  SPEAKER_00: The study's main contribution is a larger and richer map of rare genetic associations, not a new treatment.
• 24:10
  SPEAKER_00: It points toward a view of primary open-angle glaucoma that includes pressure and aqueous outflow, but also connective tissue remodeling, cellular stress responses, metabolism, and retinal neuron vulnerability.
• 24:24
  SPEAKER_00: The clearest near-term research opportunity is carefully targeted modulation of mTOR-linked autophagy and mitochondrial quality control.
• 24:32
  SPEAKER_00: It has the strongest convergence between human genetics and experimental glaucoma research.
• 24:38
  SPEAKER_00: Even so, the genetics does not tell researchers which mTOR component to target, when to treat, or what level of inhibition would be safe.
• 24:46
  SPEAKER_00: DDR2 is a cautionary example.
• 24:49
  SPEAKER_00: Its rare loss of function association suggests that inhibiting the target with an existing drug might be counterproductive.
• 24:55
  SPEAKER_00: The MAMPT result is intriguing, but too indirect to justify anti-Tau treatment for glaucoma.
• 25:02
  SPEAKER_00: For patients, the practical message is simple.
• 25:05
  SPEAKER_00: None of these results supports changing current glaucoma treatment or taking a cancer, immune suppressing, or Alzheimer's drug for glaucoma.
• 25:13
  SPEAKER_00: The findings justify further laboratory work and eventually carefully designed clinical studies, not self-treatment.
• 25:20
  SPEAKER_00: Which new glaucoma gene is most likely to lead to a treatment?
• 25:24
  SPEAKER_00: MTOR ranks first, but the most promising hypothesis is narrower than give people an MTOR inhibitor.
• 25:31
  SPEAKER_00: It is that restoring a healthy balance of autophagy and mitochondrial cleanup in retinal ganglion cells may slow neural damage.
• 25:38
  SPEAKER_00: The genetics, experimental glaucoma research, and availability of locally delivered mTOR pathway medicines make this the best supported treatment direction so far.
• 25:48
  SPEAKER_00: The correct dose, drug and delivery method remain unknown.
• 25:52
  SPEAKER_00: ANGPTL7 ranks next as an outflow-focused opportunity, followed by LTBP2 and DDR2 as extracellular matrix candidates.
• 26:01
  SPEAKER_00: But the DDR2 genetics argues for caution with inhibitors, and neither LTBP2 nor the rare variant discoveries in stress response genes yet point to a clear repurposed medicine.
• 26:13
  SPEAKER_00: MAPT and LIN are lower ranked because their causal roles and treatment directions are less certain.
• 26:19
  SPEAKER_00: Bottom line, the study provides credible biological clues and a short list for follow-up.
• 26:24
  SPEAKER_00: It does not yet show that an existing drug can safely prevent glaucoma-related vision loss.
• 26:30
  SPEAKER_00: MTOR-linked autophagy is the leading hypothesis to test, not a treatment patients should use today.
• 26:36
  SPEAKER_00: All links to sources are available in the text version of this article.
• 26:40
  SPEAKER_00: You can find the full article at VisualFieldTest.com.
• 26:44
  SPEAKER_00: Thanks for listening.
• 26:45
  SPEAKER_00: To check your visual field, click the link at the bottom of this article or visit visualfieldtest.com.