Mesenchymal stromal/stem cells (MSCs) and their secreted factors have been shown to have immunomodulatory and regenerative effects. In this study, we investigated human bone-marrow-derived MSC secretome (MSC-S) for the treatment of corneal epithelial wounds. Specifically, we evaluated the role of MSC extracellular vesicles (EV)/exosomes in mediating the wound-healing effects of the MSC-S. In vitro studies using human corneal epithelial cells showed that MSC-CM increased cell proliferation in HCEC and HCLE cells, while EV-depleted MSC-CM showed lower cell proliferation in both cell lines compared to the MSC-CM group. In vitro and in vivo experiments revealed that 1X MSC-S consistently promoted wound healing more effectively than 0.5X MSC-S, and MSC-CM promoted wound healing in a dose-dependent manner, while exosome deprivation delayed wound healing. We further evaluated the incubation period of MSC-CM on corneal wound healing and showed that MSC-S collected for 72 h is more effective than MSC-S collected for 48 h. Finally, we evaluated the stability of MSC-S under different storage conditions and found that after one cycle of freeze–thawing, MSC-S is stable at 4 °C for up to 4 weeks. Collectively, we identified the following: (i) MSC-EV/Exo as the active ingredient in MSC-S that mediates the wound-healing effects in the corneal epithelium, providing a measure to optimize its dosing for a potential clinical product; (ii) Treatment with EV/Exo-containing MSC-S resulted in an improved corneal barrier and decreased corneal haze/edema relative to EV/Exo-depleted MSC-S; (iii) The stability of MSC-CM for up to 4 weeks showed that the regular storage condition did not significantly impact its stability and therapeutic functions.

Pharmacological induction of wild-type PAX6 allele improved ocular abnormalities induced by PAX6 haploinsufficiency in mice.

Nociceptors respond to noxious stimuli and transmit pain signals to the central nervous system. In the cornea, the nociceptors located in the most external layer provide a myriad of sensation modalities. Damage to these corneal nerve fibers can induce neuropathic pain. In response, corneal nerves become sensitized to previously non-noxious stimuli. Assessing corneal pain origin is a complex ophthalmic challenge due to variations in its causes and manifestations. Current FDA-approved therapies for corneal nociceptive pain, such as acetaminophen and NSAIDs, provide only broad-acting relief with unwanted side effects, highlighting the need for precision medicine for corneal nociceptive pain. A few targeted treatments, including perfluorohexyloctane (F6H8) eye drops and Optive Plus (TRPV1 antagonist), are FDA-approved, while others are in preclinical development. Treatments that target signaling pathways related to neurotrophic factors, such as nerve growth factors and ion channels, such as the transient receptor potential (TRP) family or tropomyosin receptor kinase A, may provide a potential combinatory therapeutic approach. This review describes the roles of nociceptors in corneal pain. In addition, it evaluates molecules within nociceptor signaling pathways for their potential to serve as targets for efficient therapeutic strategies for corneal nociceptive pain aimed at modulating neurotrophic factors and nociceptive channel sensitivity.

Dry eye disease (DED) is an ocular surface disorder characterized by tear film instability, inflammation, epithelial damage, and neurosensory abnormalities. Due to its multifactorial etiology and pathophysiology, conventional therapies that focus on lubrication and immunosuppression often fall short in addressing the neuropathic component of ocular pain experienced by a growing subset of patients. Recent developments in sensory neuroscience have highlighted the pivotal role of ion channels in mediating ocular surface homeostasis, pain signaling, and inflammation. This review examines the role of the following major ion channel families in the pathophysiology of DED and neuropathic ocular pain: transient receptor potential (TRP) channels, voltage-gated sodium (Nav) channels, and purinergic P2X receptors. The review details their anatomical distribution, molecular function, and responses to environmental stimuli such as heat, cold, osmolarity, and injury. Current treatments, such as artificial tears, anti-inflammatory drops, and systemic neuromodulators, are also reviewed in relation to their effects on ion channel modulation. Additionally, emerging therapies that directly target sensory transduction pathways are introduced. This review highlights the therapeutic potential of ion channel modulation in personalizing treatment for patients with ocular surface pain, particularly those with neuropathic features unresponsive to standard care.