The multifunctional human ocular melanocortin system

Wu, Chieh‐Lin; Cioanca, Adrian V.; Gelmi, Maria Chiara; Wen, Li; Girolamo, Nick Di; Zhu, Ling; Natoli, Riccardo; Conway, R Max; Petsoglou, Constantinos; Jager, Martine J.; McCluskey, Peter; Madigan, Michele C.

doi:10.1016/j.preteyeres.2023.101187

Cited by 9 publications

(6 citation statements)

References 224 publications

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“…ARPE‐19 cells were chosen for follow‐up experiments since they are one of the key cells in the pathogenesis of VKH disease and pigment is thought to play an antigenic role in VKH development. [ 8 , 10 ] These results suggested that OR11H1 might play an important functional role in the development of uveitis.…”

Section: Resultsmentioning

confidence: 87%

“…[ 4 , 5 ] The retinal pigment epithelium (RPE) is a monolayer of pigment cells that is involved in the pathological process of VKH disease. [ 6 , 7 , 8 , 9 ] Long‐held theories suggest that the symptoms of VKH disease may be caused by an autoimmune response to melanin. [ 4 , 7 ] In the early stage of VKH disease, human melanoma cells are severely affected by T cells, presenting as folds of RPE.…”

Section: Introductionmentioning

confidence: 99%

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OR11H1 Missense Variant Confers the Susceptibility to Vogt‒Koyanagi‒Harada Disease by Mediating Gadd45g Expression

Li,

Wang,

Wang

et al. 2024

Advanced Science

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Vogt‒Koyanagi‒Harada (VKH) disease is a severe autoimmune disease. Herein, whole‐exome sequencing (WES) study are performed on 2,573 controls and 229 VKH patients with follow‐up next‐generation sequencing (NGS) in a collection of 2,380 controls and 2,278 VKH patients. A rare c.188T>C (p Val63Ala) variant in the olfactory receptor 11H1 (OR11H1) gene is found to be significantly associated with VKH disease (rs71235604, Pcombined = 7.83 × 10−30, odds ratio = 3.12). Functional study showes that OR11H1‐A63 significantly increased inflammatory factors production and exacerbated barrier function damage. Further studies using RNA‐sequencing find that OR11H1‐A63 markedly increased growth arrest and DNA‐damage‐inducible gamma (GADD45G) expression. Moreover, OR11H1‐A63 activates the MAPK and NF‐κB pathways, and accelerates inflammatory cascades. In addition, inhibiting GADD45G alleviates inflammatory factor secretion, likely due to the regulatory effect of GADD45G on the MAPK and NF‐κB pathways. Collectively, this study suggests that the OR11H1‐A63 missense mutation may increase susceptibility to VKH disease in a GADD45G‐dependent manner.

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Section: Resultsmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

OR11H1 Missense Variant Confers the Susceptibility to Vogt‒Koyanagi‒Harada Disease by Mediating Gadd45g Expression

Li,

Wang,

Wang

et al. 2024

Advanced Science

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“…An important source of α-MSH is the RPE, which influences the activity of immune cells within the retina. In addition, α-MSH may well play an important role in promoting retinal cell development and viability, along with inhibiting signals of apoptosis [14,[38][39][40][41][42]. Therefore, augmenting the melanocortin pathways with α-MSH may provide a strong signal for the survival and preservation of retinal tissues under inflammatory or stressful conditions.…”

Section: Discussionmentioning

confidence: 99%

Alpha-Melanocyte-Stimulating Hormone Maintains Retinal Homeostasis after Ischemia/Reperfusion

Ng,

Cho,

Zhao

et al. 2024

Biomolecules

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Augmenting the natural melanocortin pathway in mouse eyes with uveitis or diabetes protects the retinas from degeneration. The retinal cells are protected from oxidative and apoptotic signals of death. Therefore, we investigated the effects of a therapeutic application of the melanocortin alpha-melanocyte-stimulating hormone (α-MSH) on an ischemia and reperfusion (I/R) model of retinal degenerative disease. Eyes were subjected to an I/R procedure and were treated with α-MSH. Retinal sections were histopathologically scored. Also, the retinal sections were immunostained for viable ganglion cells, activated Muller cells, microglial cells, and apoptosis. The I/R caused retinal deformation and ganglion cell loss that was significantly reduced in I/R eyes treated with α-MSH. While α-MSH treatment marginally reduced the number of GFAP-positive Muller cells, it significantly suppressed the density of Iba1-positive microglial cells in the I/R retinas. Within one hour after I/R, there was apoptosis in the ganglion cell layer, and by 48 h, there was apoptosis in all layers of the neuroretina. The α-MSH treatment significantly reduced and delayed the onset of apoptosis in the retinas of I/R eyes. The results demonstrate that therapeutically augmenting the melanocortin pathways preserves retinal structure and cell survival in eyes with progressive neuroretinal degenerative disease.

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“…Melanocortin receptor-targeting peptide has potential translational value as an alternative to non-steroidal drugs in the treatment of DED. The endogenous melanocortin neuropeptide α-melanocyte-stimulating hormone (α-MSH) is secreted by the RPE, ciliary epithelium, and iris and circulates in the anterior chamber and vitreous ( 120 ). Structurally, melanocortin peptides share the core sequence HFRW, which is essential for binding to the receptors ( 121 ).…”

Section: The Application Strategies Of Immunopeptides In Ocular Diseasesmentioning

confidence: 99%

Immunopeptides: immunomodulatory strategies and prospects for ocular immunity applications

Tang,

Qu,

Ning

et al. 2024

Front. Immunol.

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Immunopeptides have low toxicity, low immunogenicity and targeting, and broad application prospects in drug delivery and assembly, which are diverse in application strategies and drug combinations. Immunopeptides are particularly important for regulating ocular immune homeostasis, as the eye is an immune-privileged organ. Immunopeptides have advantages in adaptive immunity and innate immunity, treating eye immune-related diseases by regulating T cells, B cells, immune checkpoints, and cytokines. This article summarizes the application strategies of immunopeptides in innate immunity and adaptive immunity, including autoimmunity, infection, vaccine strategies, and tumors. Furthermore, it focuses on the mechanisms of immunopeptides in mediating ocular immunity (autoimmune diseases, inflammatory storms, and tumors). Moreover, it reviews immunopeptides’ application strategies and the therapeutic potential of immunopeptides in the eye. We expect the immune peptide to get attention in treating eye diseases and to provide a direction for eye disease immune peptide research.

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The multifunctional human ocular melanocortin system

Cited by 9 publications

References 224 publications

OR11H1 Missense Variant Confers the Susceptibility to Vogt‒Koyanagi‒Harada Disease by Mediating Gadd45g Expression

OR11H1 Missense Variant Confers the Susceptibility to Vogt‒Koyanagi‒Harada Disease by Mediating Gadd45g Expression

Alpha-Melanocyte-Stimulating Hormone Maintains Retinal Homeostasis after Ischemia/Reperfusion

Immunopeptides: immunomodulatory strategies and prospects for ocular immunity applications

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