# Role of Growth Hormone (GH) and Other Somatotropic Axis Elements in Retinal Neuroprotection

**Authors:** David Epardo, Carlos Arámburo, Carlos Guillermo Martínez-Moreno

PMC · DOI: 10.3390/cimb48030296 · 2026-03-11

## TL;DR

This paper explores how growth hormone and related molecules may protect the retina from degeneration and could be used as new treatments for retinal diseases.

## Contribution

The paper highlights new evidence that growth hormone has neuroprotective effects in retinal injury, challenging previous assumptions.

## Key findings

- Growth hormone treatment has strong neuroprotective effects during retinal injury.
- Other molecules in the GH axis may also contribute to retinal protection.
- Existing evidence suggests GH axis research could lead to new therapies for retinal degeneration.

## Abstract

Various pathological conditions can result in retinal degeneration and, in extreme cases, blindness. Unfortunately, current treatments for many of these conditions are not effective, and ongoing research encounters numerous obstacles due to the complex nature of these diseases, which involve multiple simultaneous mechanisms that cannot be controlled by a single factor. Therefore, there is an urgent need to propose and test new molecules that could exert protective effects at multiple levels. Traditionally, growth hormone (GH) has been viewed as a detrimental factor contributing to develop retinopathies. However, recent investigation has debunked this notion, revealing that GH treatment exerts strong neuroprotective effects during retinal injury. It is crucial to recognize that these actions are not exclusive to GH, since other related molecules may also be involved. Therefore, it is important to collect relevant existing evidence regarding GH axis translational research in order to understand its potential as a therapeutic option for retinal degeneration.

## Linked entities

- **Proteins:** GH1 (growth hormone 1)
- **Diseases:** retinal degeneration (MONDO:0004580)

## Full-text entities

- **Genes:** LHCGR (luteinizing hormone/choriogonadotropin receptor) [NCBI Gene 395776] {aka cLH-R}, SSTR4 (somatostatin receptor 4) [NCBI Gene 6754] {aka SS-4-R, SS4-R, SS4R, SST4}, BDNF (brain derived neurotrophic factor) [NCBI Gene 396186], IGF1 (insulin like growth factor 1) [NCBI Gene 418090] {aka IGF-1, IGF-I}, JAK3 (Janus kinase 3) [NCBI Gene 395845] {aka JAK}, Bcl2 (B cell leukemia/lymphoma 2) [NCBI Gene 12043] {aka Bcl-2, C430015F12Rik, D630044D05Rik, D830018M01Rik}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 395909] {aka VEGF}, Ccl2 (C-C motif chemokine ligand 2) [NCBI Gene 24770] {aka MCP-1, MCP1, Scya2, Sigje}, SSTR3 (somatostatin receptor 3) [NCBI Gene 427907] {aka SS3R}, Ghrh (growth hormone releasing hormone) [NCBI Gene 14601] {aka GRF, Ghrf}, Actb (actin, beta) [NCBI Gene 11461] {aka Actx, E430023M04Rik, beta-actin}, STAT5a [NCBI Gene 100755571], SIRPA (signal regulatory protein alpha) [NCBI Gene 140885] {aka BIT, CD172A, MFR, MYD-1, MYD1, P84}, Igf1 (insulin-like growth factor 1) [NCBI Gene 24482] {aka IGF}, TNFRSF1A (TNF receptor superfamily member 1A) [NCBI Gene 7132] {aka CD120a, FPF, TBP1, TNF-R, TNF-R-I, TNF-R55}, STAT5A (signal transducer and activator of transcription 5A) [NCBI Gene 395556] {aka STAT5, STAT5B}, GDNF (glial cell derived neurotrophic factor) [NCBI Gene 2668] {aka ATF, ATF1, ATF2, HFB1-GDNF, HSCR3}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, NLGN1 (neuroligin 1) [NCBI Gene 424980] {aka neuroligin-1}, SERPINF1 (serpin family F member 1) [NCBI Gene 5176] {aka EPC-1, OI12, OI6, PEDF, PIG35}, 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}, GAP43 (growth associated protein 43) [NCBI Gene 427955] {aka GAP-43}, Igf1 (insulin-like growth factor 1) [NCBI Gene 16000] {aka C730016P09Rik, Igf-1, Igf-I}, Sstr3 (somatostatin receptor 3) [NCBI Gene 20607] {aka Smstr-3, Smstr3, sst3}, STAT3 [NCBI Gene 100755865], NTF3 (neurotrophin 3) [NCBI Gene 4908] {aka HDNF, NGF-2, NGF2, NT-3, NT3}, FGF2 (fibroblast growth factor 2) [NCBI Gene 396413] {aka BFGF, FGF-2, HBGF-2}, insulin receptor substrate-2 [NCBI Gene 428017], Gnrhr (gonadotropin releasing hormone receptor) [NCBI Gene 14715], Ghrhr (growth hormone releasing hormone receptor) [NCBI Gene 14602] {aka Ghrfr, lit, little}, TNFRSF1B (TNF receptor superfamily member 1B) [NCBI Gene 7133] {aka CD120b, TBPII, TNF-R-II, TNF-R75, TNFBR, TNFR1B}, Sst (somatostatin) [NCBI Gene 20604] {aka SOM, SRIF, SS, Smst}, TRHR (thyrotropin releasing hormone receptor) [NCBI Gene 395770], Sstr4 (somatostatin receptor 4) [NCBI Gene 20608] {aka Smstr4, sst4}, TRH (thyrotropin releasing hormone) [NCBI Gene 7200] {aka Pro-TRH, TRF}, NGF (nerve growth factor) [NCBI Gene 396466] {aka NGFB, beta-NGF}, NOTCH2 (notch receptor 2) [NCBI Gene 4853] {aka AGS2, HJCYS, hN2}, Prl (prolactin) [NCBI Gene 19109] {aka Gha1, Prl1a1}, Trhr (thyrotropin releasing hormone receptor) [NCBI Gene 22045] {aka TRH-R1}, ZHX2 (zinc fingers and homeoboxes 2) [NCBI Gene 22882] {aka AFR1, RAF}, Ghrh (growth hormone releasing hormone) [NCBI Gene 29446] {aka GHRF}, GNRH1 (gonadotropin releasing hormone 1) [NCBI Gene 2796] {aka GNRH, GRH, LHRH, LNRH}, CTSD (cathepsin D) [NCBI Gene 396090], Pik3cb (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta) [NCBI Gene 85243], GHSR (growth hormone secretagogue receptor) [NCBI Gene 378911], GNRHR3 (gonadotropin releasing hormone receptor 3) [NCBI Gene 427517] {aka GNRHR, GNRHR1/III, GNRHR2, cGnRH-R-III}, CNTF (ciliary neurotrophic factor) [NCBI Gene 1270] {aka HCNTF}, TRH (thyrotropin releasing hormone) [NCBI Gene 414344] {aka Pro-TRH}, Growth Hormone Receptor [NCBI Gene 107049315], GHRHR (growth hormone releasing hormone receptor) [NCBI Gene 420385], GHRL (ghrelin/obestatin prepropeptide) [NCBI Gene 408185] {aka ghrelin, preproghrelin}, SST (somatostatin) [NCBI Gene 6750] {aka SMST, SST1}, IGF1R (insulin like growth factor 1 receptor) [NCBI Gene 395889] {aka IGF-1R}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, GNRH1 (gonadotropin releasing hormone 1) [NCBI Gene 770134] {aka CGNRH-I, GnRH-1, GnRH-I, GnRHI, LHRH-I}, HSPG2 (heparan sulfate proteoglycan 2) [NCBI Gene 3339] {aka HSPG, PLC, PRCAN, SJA, SJS, SJS1}, Rps18 (ribosomal protein S18) [NCBI Gene 20084] {aka H-2Ke3, H2-Ke3, Ke-3, ke3}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, GHRH (growth hormone releasing hormone) [NCBI Gene 2691] {aka GHRF, GRF, INN}, SRC (SRC proto-oncogene, non-receptor tyrosine kinase) [NCBI Gene 6714] {aka ASV, SRC1, THC6, c-SRC, p60-Src}
- **Diseases:** excitotoxic damage (MESH:D020263), thyroid-associated ophthalmopathy (MESH:D049970), neuroinflammation (MESH:D000090862), axonopathies (MESH:D016472), retinopathies (MESH:D058437), ischemia (MESH:D007511), deficient (MESH:D007153), diabetic (MESH:D003920), neurodegeneration (MESH:D019636), Retinal injury (MESH:D012173), glaucoma (MESH:D005901), infections (MESH:D007239), phototoxicity (MESH:D017484), optic nerve crush injury (MESH:D020221), excitotoxic injury (MESH:D014947), demyelinating optic neuritis (MESH:D009902), DR (MESH:D003930), acute injury (MESH:D001930), retinal degeneration (MESH:D012162), neural damage (MESH:D015441), retinitis pigmentosa (MESH:D012174), corneal diseases (MESH:D003316), ONC (MESH:D000080344), hyperglycemia (MESH:D006943), neurologically compromised (MESH:D009461), hypoxic (MESH:D002534), ischemic injury (MESH:D017202), neuronal death (MESH:D009410), lens injury (MESH:D007905), inflammation (MESH:D007249), GH (MESH:D004393), Retinal Diseases (MESH:D012164), open-angle glaucoma (MESH:D005902), crush (MESH:D003444), thyroid autoimmunity (MESH:D013967), congenital disorders (MESH:D009358), ischemic (MESH:D002545), metabolic diseases (MESH:D008659), blindness (MESH:D001766), RGC loss (MESH:D016388), optic neuropathies (MESH:D009901), cerebral palsy (MESH:D002547), tissue damage (MESH:D017695), ocular dysfunctions (MESH:D005128), deficits in the visual system (MESH:D014786), proliferative diabetic retinopathy (OMIM:603933), acromegalic (MESH:D000172)
- **Chemicals:** KA (MESH:D007608), zymosan (MESH:D015054), GABA (MESH:D005680), BioRender (-), octreotide (MESH:D015282), GH (MESH:D013006), LPS (MESH:D008070), dopamine (MESH:D004298), pituitary (MESH:D010907), melatonin (MESH:D008550), serotonin (MESH:D012701), Acetylcholine (MESH:D000109)
- **Species:** Gallus gallus (bantam, species) [taxon 9031], Homo sapiens (human, species) [taxon 9606], Cavia porcellus (domestic guinea pig, species) [taxon 10141], Cyprinus carpio (carp, species) [taxon 7962], Bos taurus (bovine, species) [taxon 9913], Mus musculus (house mouse, species) [taxon 10090], Cercopithecidae (monkey, family) [taxon 9527], Coturnix coturnix (Common quail, species) [taxon 9091], Carassius auratus (goldfish, species) [taxon 7957], Ctenopharyngodon idella (grass carp, species) [taxon 7959], Rattus norvegicus (brown rat, species) [taxon 10116]
- **Mutations:** S179D
- **Cell lines:** GSE199317 — Konosirus punctatus (Dotted gizzard shad), Spontaneously immortalized cell line (CVCL_6F81), QNR/D — Coturnix japonica (Japanese quail), Quail fibrosarcoma, Cancer cell line (CVCL_T464), 3T3-F442A — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0122), Chinese hamster ovary — Cricetulus griseus (Chinese hamster), Spontaneously immortalized cell line (CVCL_0213)

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13024951/full.md

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Source: https://tomesphere.com/paper/PMC13024951