CD11b+GR1+ Myeloid Cells Secrete NGF and Promote Trigeminal Ganglion Neurite Growth: Implications for Corneal Nerve Regeneration

Sarkar, Joy; Chaudhary, Shweta; Jassim, Sarmad; Ozturk, Okan; Chamon, Wallace; Ganesh, Balaji; Tibrewal, Sapna; Gandhi, Sonal; Byun, Yong-Soo; Hallak, Joelle; Mahmud, Dolores; Mahmud, Nadim; Rondelli, Damiano; Jain, Sandeep

doi:10.1167/iovs.13-12237

Cited by 39 publications

(32 citation statements)

References 58 publications

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“…While the epithelium-wound closure was delayed for several hours, we observed significantly less nerve regeneration in DC-depleted corneas, compared to control corneas. Recently, Sarkar et al reported that CD11b+GR1+ myeloid cells secrete NGF and promote trigeminal ganglion neurite growth49. It is possible that elevated NGF and CNTF and/or the infiltrated cells expressing them are required for proper nerve regeneration in the cornea.…”

Section: Discussionmentioning

confidence: 99%

Intraepithelial dendritic cells and sensory nerves are structurally associated and functional interdependent in the cornea

Gao

Lee

2016

Sci Rep

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The corneal epithelium consists of stratified epithelial cells, sparsely interspersed with dendritic cells (DCs) and a dense layer of sensory axons. We sought to assess the structural and functional correlation of DCs and sensory nerves. Two morphologically different DCs, dendriform and round-shaped, were detected in the corneal epithelium. The dendriform DCs were located at the sub-basal space where the nerve plexus resides, with DC dendrites crossing several nerve endings. The round-shaped DCs were closely associated with nerve fiber branching points, penetrating the basement membrane and reaching into the stroma. Phenotypically, the round-shaped DCs were CD86 positive. Trigeminal denervation resulted in epithelial defects with or without total tarsorrhaphy, decreased tear secretion, and the loss of dendriform DCs at the ocular surface. Local DC depletion resulted in a significant decrease in corneal sensitivity, an increase in epithelial defects, and a reduced density of nerve endings at the center of the cornea. Post-wound nerve regeneration was also delayed in the DC-depleted corneas. Taken together, our data show that DCs and sensory nerves are located in close proximity. DCs may play a role in epithelium innervation by accompanying the sensory nerve fibers in crossing the basement membrane and branching into nerve endings.

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Section: Discussionmentioning

confidence: 99%

Intraepithelial dendritic cells and sensory nerves are structurally associated and functional interdependent in the cornea

Gao

Lee

2016

Sci Rep

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“…Nerve growth factor (NGF) is the first-discovered member of the neurotrophin gene family, which is involved in the growth and survival of nerves (44). NGF in the cornea has been thought to play a role in promoting corneal nerve regeneration (45). In the context of wound healing, NGF is known to accelerate wound healing by promoting cell cycle progression and by increasing cell migration (46,47).…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoid action in human corneal epithelial cells establishes roles for corticosteroids in wound healing and barrier function of the eye

Kadmiel

Jànoshàzi

et al. 2016

Experimental Eye Research

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Glucocorticoids play diverse roles in almost all physiological systems of the body, including both anti-inflammatory and immunosuppressive roles. Synthetic glucocorticoids are one of the most widely prescribed drugs and are used in the treatment of conditions such as autoimmune diseases, allergies, ocular disorders and certain types of cancers. In the interest of investigating glucocorticoid actions in the cornea of the eye, we established that multiple cell types in mouse corneas express functional glucocorticoid receptor (GR) with corneal epithelial cells having robust expression. To define glucocorticoid actions in a cell type-specific manner, we employed immortalized human corneal epithelial (HCE) cell line to define the glucocorticoid transcriptome and elucidated its functions in corneal epithelial cells. Over 4000 genes were significantly regulated within 6 hours of dexamethasone treatment, and genes associated with cell movement, cytoskeletal remodeling and permeability were highly regulated. Real-time in vitro wound healing assays revealed that glucocorticoids delay wound healing by attenuating cell migration. These functional alterations were associated with cytoskeletal remodeling at the wounded edge of a scratch-wounded monolayer. However, glucocorticoid treatment improved the organization of tight-junction proteins and enhanced the epithelial barrier function. Our results demonstrate that glucocorticoids profoundly alter corneal epithelial gene expression and many of these changes likely impact both wound healing and epithelial cell barrier function.

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“…60 The thy1-YFP transgenic mouse model developed by Joshua Sanes' group 61 which exhibits yellow fluorescent nerves in the cornea has provided an amazing tool to basic and translational scientists to study corneal nerves in vivo and studies using this model have yielded numerous breakthroughs and publications in the field of corneal nerve injury and regeneration research. 7,[62][63][64] These studies have highlighted neurotoxicity in the eye due to preservatives like benzalkonium chloride and augmented the move towards non-neurotoxic preservative-free eye-drops, 62 the presence of inflammatory CD11b+GR1+myeloid-derived suppressor cells which play an important role in nerve regeneration, 65 the importance of VEGF-B in stimulating peripheral nerve growth, etc. 63 This greater clarity and continued progress in our understanding of the functional and structural alterations of nerves in normal and disease states and their correlation with clinical signs and symptoms is crucial for the further development of targeted drug therapy and treatments for debilitating corneal diseases.…”

Section: Corneal Nerve Researchmentioning

confidence: 99%

Recent Perspectives on Corneal Nerves: A Short Review

Sarkar¹

2017

Ophthalmol Open J

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This mini-review provides an overview of recent trends in our understanding of the general structure of the cornea, the importance of corneal nerves, their function and distribution in the different layers of the cornea based on reports obtained by imaging techniques such as in vivo confocal microscopy (IVCM) and immunohistochemistry (IHC) analysis. Recent data on corneal nerve status in conditions such as Dry Eye Disease (DED) and Diabetes is also discussed. There is additional emphasis on corneal nerve damage due to injury especially during surgical interventions and underlying disease states as well as translational research on corneal nerve regeneration. Information on recent clinical studies on the effect of laser corneal surgery and its impact on corneal nerves is also presented.

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CD11b+GR1+ Myeloid Cells Secrete NGF and Promote Trigeminal Ganglion Neurite Growth: Implications for Corneal Nerve Regeneration

Cited by 39 publications

References 58 publications

Intraepithelial dendritic cells and sensory nerves are structurally associated and functional interdependent in the cornea

Intraepithelial dendritic cells and sensory nerves are structurally associated and functional interdependent in the cornea

Glucocorticoid action in human corneal epithelial cells establishes roles for corticosteroids in wound healing and barrier function of the eye

Recent Perspectives on Corneal Nerves: A Short Review

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