# Research Advances in Glanimal Models of Glaucoma: Exploring Multidimensional Mechanisms and Novel Therapeutic Strategies

**Authors:** Jinshen Liu, Hui Zhang, Jiaqi Chen, Jiamin Zhou, Yujia Yu, Feng Cheng, Jie Bao, Chunhan Feng, Xiangqu Yu, Zhao Xia, Rao Ding, Zhonghui Li, Xiang Li

PMC · DOI: 10.3390/pharmaceutics18020152 · Pharmaceutics · 2026-01-25

## TL;DR

This review summarizes recent advances in glaucoma animal models, highlighting their role in understanding disease mechanisms and developing new treatments.

## Contribution

The paper systematically compiles recent developments in glanimal models and outlines future directions for standardization and integration of therapies.

## Key findings

- Glanimal models replicate various glaucoma pathogenic mechanisms like mechanical stress and inflammation.
- These models are key for testing neuroprotection and anti-fibrotic therapies.
- Future trends include model standardization and integration with advanced imaging and drug delivery systems.

## Abstract

Objective: Glaucoma is a complex optic neuropathy characterized by the progressive loss of retinal ganglion cells (RGCs). Animal models are crucial tools for deciphering its multidimensional pathogenesis and evaluating novel therapeutic strategies. This review aims to systematically summarize the establishment methods, application advances, and future development trends of various glanimal models. Methods: The literature for this review was identified through systematic searches of electronic databases, including PubMed, Web of Science Core Collection, and Google Scholar. The search strategy utilized a combination of keywords and their variants: “glaucoma”, “animal models”, “retinal ganglion cells”, “intraocular pressure”, “neuroprotection”, “immune inflammation”, “fibrosis”, and “filtration surgery”. The search focused on articles published between 2015 and 2025 to cover the major advances of the last decade. The scope encompassed original research articles, reviews, and meta-analyses. Results: Diverse glanimal models successfully replicate different facets of glaucoma, elucidating multidimensional pathogenesis involving mechanical stress, immune inflammation, excitotoxicity, oxidative stress, and fibrosis. These models have played an indispensable role in screening neuroprotective agents, evaluating anti-fibrotic strategies, and validating the application of advanced imaging and functional assessment technologies. Current research is evolving towards model standardization, multi-factor simulation, and the integration of novel drug delivery systems and immunomodulatory strategies. Conclusions: The diversification of glanimal models provides a powerful platform for in-depth investigation of disease mechanisms and the development of innovative therapies. Future research should focus on establishing standardized models that better mimic the clinical pathological state and deeply integrating multimodal assessment technologies with targeted therapies. This will facilitate the translation of basic research into clinical applications, ultimately achieving personalized precision medicine for glaucoma.

## Linked entities

- **Diseases:** glaucoma (MONDO:0005041)

## Full-text entities

- **Genes:** FABP5 (fatty acid binding protein 5) [NCBI Gene 2171] {aka E-FABP, EFABP, KFABP, PA-FABP, PAFABP}, Tgfb2 (transforming growth factor, beta 2) [NCBI Gene 81809] {aka TGF-B2}, DLG4 (discs large MAGUK scaffold protein 4) [NCBI Gene 1742] {aka MRD62, PSD95, SAP-90, SAP90}, Rag1 (recombination activating 1) [NCBI Gene 19373] {aka Rag-1}, GRIN2B (glutamate ionotropic receptor NMDA type subunit 2B) [NCBI Gene 2904] {aka DEE27, EIEE27, GluN2B, MRD6, NMDAR2B, NR2B}, C1qa (complement component 1, q subcomponent, alpha polypeptide) [NCBI Gene 12259] {aka Adic, C1q}, C3ar1 (complement component 3a receptor 1) [NCBI Gene 12267] {aka AZ3B, C3AR, HNFAG09}, GPX4 (glutathione peroxidase 4) [NCBI Gene 2879] {aka GPx-4, GSHPx-4, MCSP, PHGPx, SMDS, snGPx}, HMGB1 (high mobility group box 1) [NCBI Gene 3146] {aka HMG-1, HMG1, HMG3, SBP-1}, PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468] {aka CIMT1, FPLD3, GLM1, NR1C3, PPARG1, PPARG2}, MMRN1 (multimerin 1) [NCBI Gene 22915] {aka ECM, EMILIN4, GPIa*, MMRN}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, SLC1A2 (solute carrier family 1 member 2) [NCBI Gene 6506] {aka DEE41, EAAT2, EIEE41, GLT-1, GLT1, HBGT}, E2F1 (E2F transcription factor 1) [NCBI Gene 1869] {aka E2F-1, RBAP1, RBBP3, RBP3}, TGFB2 (transforming growth factor beta 2) [NCBI Gene 7042] {aka CAEND2, G-TSF, LDS4, TGF-beta2}, Ltbp2 (latent transforming growth factor beta binding protein 2) [NCBI Gene 16997], ATF3 (activating transcription factor 3) [NCBI Gene 467], Tgfb2 (transforming growth factor, beta 2) [NCBI Gene 21808] {aka Tgf-beta2, Tgfb-2}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, BCL2L1 (BCL2 like 1) [NCBI Gene 598] {aka BCL-XL/S, BCL2L, BCLX, Bcl-X, PPP1R52}, Creb1 (cAMP responsive element binding protein 1) [NCBI Gene 81646] {aka Creb}, Fn1 (fibronectin 1) [NCBI Gene 25661] {aka FIBNEC, fn-1}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 21803] {aka TGF-beta1, TGFbeta1, Tgfb, Tgfb-1}, CCR5 (C-C motif chemokine receptor 5) [NCBI Gene 1234] {aka CC-CKR-5, CCCKR5, CCR-5, CD195, CKR-5, CKR5}, MZB1 (marginal zone B and B1 cell specific protein) [NCBI Gene 51237] {aka MEDA-7, PACAP, pERp1}, Cd247 (CD247 antigen) [NCBI Gene 12503] {aka 4930549J05Rik, A430104F18Rik, Cd3, Cd3-eta, Cd3-zeta, Cd3h}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}, RIPK1 (receptor interacting serine/threonine kinase 1) [NCBI Gene 8737] {aka AIEFL, IMD57, RIP, RIP-1, RIP1}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, CCL5 (C-C motif chemokine ligand 5) [NCBI Gene 6352] {aka D17S136E, RANTES, SCYA5, SIS-delta, SISd, TCP228}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, GDNF (glial cell derived neurotrophic factor) [NCBI Gene 2668] {aka ATF, ATF1, ATF2, HFB1-GDNF, HSCR3}, Il18 (interleukin 18) [NCBI Gene 16173] {aka Igif, Il-18}, REN (renin) [NCBI Gene 5972] {aka ADTKD4, HNFJ2, RTD}, ERG (ETS transcription factor ERG) [NCBI Gene 2078] {aka LMPHM14, erg-3, p55}, S100A9 (S100 calcium binding protein A9) [NCBI Gene 6280] {aka 60B8AG, CAGB, CFAG, CGLB, L1AG, LIAG}, Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 18708] {aka PI3K, p50alpha, p55alpha, p85alpha}, BMP4 (bone morphogenetic protein 4) [NCBI Gene 652] {aka BMP2B, BMP2B1, MCOPS6, OFC11, ZYME}, RIPK3 (receptor interacting serine/threonine kinase 3) [NCBI Gene 11035] {aka RIP3}, C3AR1 (complement C3a receptor 1) [NCBI Gene 719] {aka AZ3B, C3AR, HNFAG09}, MLKL (mixed lineage kinase domain like pseudokinase) [NCBI Gene 197259] {aka hMLKL}, BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, Ripk3 (receptor-interacting serine-threonine kinase 3) [NCBI Gene 56532] {aka 2610528K09Rik, Rip3}, EDN1 (endothelin 1) [NCBI Gene 1906] {aka ARCND3, ET1, HDLCQ7, PPET1, QME}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 59086] {aka Tgfb}, SPP1 (secreted phosphoprotein 1) [NCBI Gene 6696] {aka BNSP, BSPI, ETA-1, OPN}, Syn1 (synapsin I) [NCBI Gene 24949], CAMK2G (calcium/calmodulin dependent protein kinase II gamma) [NCBI Gene 818] {aka CAMK, CAMK-II, CAMKG, MRD59}, Tbk1 (TANK-binding kinase 1) [NCBI Gene 56480] {aka 1200008B05Rik}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, CNTF (ciliary neurotrophic factor) [NCBI Gene 1270] {aka HCNTF}, Trav6-3 (T cell receptor alpha variable 6-3) [NCBI Gene 328483] {aka Gm13948, Gm193, Gm4, TCR}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, CYBB (cytochrome b-245 beta chain) [NCBI Gene 1536] {aka AMCBX2, CGD, CGDX, GP91-1, GP91-PHOX, GP91PHOX}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}
- **Diseases:** AD (MESH:C537791), axonal injury (MESH:D001480), angle-closure glaucoma (MESH:D015812), necrosis (MESH:D009336), Nerve Crush (MESH:D003444), immune dysregulation (OMIM:614878), visual field defect (MESH:D005128), retinal damage (MESH:D012164), GFS (MESH:D005901), congenital glaucoma (MESH:C565547), glaucomatous pathological (MESH:D005598), ocular hypertension (MESH:D009798), RGC degeneration (MESH:D009410), IOP elevation (MESH:D019586), retinal capillary degeneration (MESH:D012162), toxicity (MESH:D064420), vascular injuries (MESH:D057772), ischemic damage (MESH:D017202), retinal excitotoxic injury (MESH:D012173), immunodeficient (MESH:D007153), RGC death (MESH:D003643), myelin injury (MESH:D003711), I/R (MESH:D015427), gliosis (MESH:D005911), retinal and optic nerve I/R injury (MESH:D018917), hypoxia (MESH:D000860), blindness (MESH:D001766), RGC damage (MESH:D020263), nerve (MESH:C537568), metabolic abnormalities (MESH:D008659), POAG (MESH:D005902), Ischemia (MESH:D007511), autoimmune (MESH:D001327), glaucomatous lesions (MESH:D009059), IOP (MESH:D064090), structural abnormalities (MESH:C566527), optic neurodegeneration (OMIM:615491), neuroinflammation (MESH:D000090862), disruption (MESH:D019958), ischemic (MESH:D002545), neurotoxicity (MESH:D020258), angle dysgenesis (MESH:C537048), neural damage (MESH:D015441), Alzheimer's disease (MESH:D000544), mitochondrial damage (MESH:D028361), Hereditary glanimal (MESH:D009386), visual dysfunction (MESH:D014786), Fibrosis (MESH:D005355), RGC loss (MESH:D016388), optic neuropathy (MESH:D009901), NTG (MESH:D057066), Inflammation (MESH:D007249), hereditary glaucoma (MESH:C580055), ONC (MESH:D000080344), Optic nerve damage (MESH:D020221), glaucomatous neurodegeneration (MESH:D019636), RGC injury (MESH:D014947)
- **Chemicals:** Dex-Ac (MESH:C018038), ROS (MESH:D017382), calcium (MESH:D002118), baicalin (MESH:C038044), TRP (MESH:D014364), beta-lactam (MESH:D047090), PLGA (MESH:D000077182), pioglitazone (MESH:D000077205), Astragaloside IV (MESH:C052064), lipid (MESH:D008055), DHA (MESH:D004281), Steroid (MESH:D013256), ursodeoxycholic acid (MESH:D014580), glutathione (MESH:D005978), GSK872 (MESH:C000633405), PCL (MESH:C016240), SB202190 (MESH:C090942), OMT (MESH:C037573), ceftriaxone (MESH:D002443), DiOHF (MESH:C529890), Pirfenidone (MESH:C093844), Magnolol (MESH:C005498), dexamethasone (MESH:D003907), MMC (MESH:D016685), josamycin (MESH:D015570), polyunsaturated fatty acid (MESH:D005231), Necrostatin-1 (MESH:C507699), melatonin (MESH:D008550), FDI-6 (-), artesunate (MESH:D000077332), glutamate (MESH:D018698), SIN (MESH:C009271), alkaloid (MESH:D000470), KYN (MESH:D007737), resveratrol (MESH:D000077185), N-methyl-D-aspartate (MESH:D016202), silicone (MESH:D012828), iron (MESH:D007501), silicone oil (MESH:D012827), water (MESH:D014867), aldosterone (MESH:D000450), paclitaxel (MESH:D017239), KYNA (MESH:D007736), zinc (MESH:D015032), HG9-91-01 (MESH:C577044), gamma-cyclodextrin (MESH:C023792), metal (MESH:D008670)
- **Species:** Oryctolagus cuniculus (domestic rabbit, species) [taxon 9986], Homo sapiens (human, species) [taxon 9606], Felis catus (cat, species) [taxon 9685], Rattus norvegicus (brown rat, species) [taxon 10116], Cercopithecidae (monkey, family) [taxon 9527], Canis lupus familiaris (dog, subspecies) [taxon 9615], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** A3 adenosine, A3 Adenosine
- **Cell lines:** /2J — Homo sapiens (Human), Transformed cell line (CVCL_N185), DBA/2J — Mus musculus (Mouse), Finite cell line (CVCL_6496)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12944598/full.md

## References

131 references — full list in the complete paper: https://tomesphere.com/paper/PMC12944598/full.md

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Source: https://tomesphere.com/paper/PMC12944598