Translational research : the journal of laboratory and clinical medicine
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Review
Immune responses to injury and their links to eye disease: Immune responses to wounding in the eye.
The eye is regarded as an immune privileged site. Since the presence of a vasculature would impair vision, the vasculature of the eye is located outside of the central light path. As a result, many regions of the eye evolved mechanisms to deliver immune cells to sites of dysgenesis, injury, or in response to the many age-related pathologies. ⋯ The response to traumatic or pathological injury is distinct in different regions of the eye. Age-related diseases impact both the anterior and posterior segment and lead to reduced quality of life and blindness. Here we focus attention on the role that inflammation and fibrosis play in the progression of age-related pathologies of the cornea and the lens as well as in glaucoma, the formation of epiretinal membranes, and in proliferative vitreoretinopathy.
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Type 2 diabetes is associated with several potential comorbidities, among them impaired wound healing, chronic ulcerations, and the requirement for lower extremity amputation. Disease-associated abnormal cellular responses, infection, immunological and microvascular dysfunction, and peripheral neuropathy are implicated in the pathogenesis of the wound healing impairment and the diabetic foot ulcer. ⋯ Better understanding of these mechanisms may provide the basis for targeted treatments for chronic diabetic wounds. This review provides an overview of wound healing pathophysiology with a focus on neural involvement in normal and diabetic wound healing, as well as future therapeutic perspectives to address the unmet needs of diabetic patients with chronic wounds.
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Although gene therapy has its conceptual origins in the treatment of Mendelian disorders, it has potential applications in regenerative medicine, including bone healing. Research into the use of gene therapy for bone healing began in the 1990s. Prior to this period, the highly osteogenic proteins bone morphogenetic protein (BMP)-2 and -7 were cloned, produced in their recombinant forms and approved for clinical use. ⋯ Data from experiments in small animal models confirm that intralesional delivery of BMP-2 cDNA is able to heal defects efficiently and safely while generating transient, local BMP-2 concentrations 2-3 log orders less than those needed by recombinant BMP-2. The next challenge is to translate this information into a clinically expedient technology for bone healing. Our present research focuses on the use of genetically modified, allografted cells and chemically modified messenger RNA.
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There is significant interest in understanding the cellular mechanisms responsible for expedited healing response in various oral tissues and how they are impacted by systemic diseases. Depending upon the types of oral tissue, wound healing may occur by predominantly re-eptihelialization, by re-epithelialization with substantial new connective tissue formation, or by a a combination of both plus new bone formation. As a result, the cells involved differ and are impacted by systemic diaseses in various ways. ⋯ In particular, diabetes inhibits the expression of mitogenic growth factors whereas that of pro-inflammatory cytokines is elevated through epigenetic mechanisms. Moreover, hyperglycemia and oxidative stress induced by diabetes prevents the expansion of mesengenic cells that are involved in both soft and hard tissue oral wounds. A better understanding of how diabetes influences the healing processes is crucial for the prevention and treatment of diabetes-associated oral complications.
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Following injury, the oral mucosa undergoes complex sequences of biological healing processes to restore homeostasis. While general similarities exist, there are marked differences in the genomics and kinetics of wound healing between the oral cavity and cutaneous epithelium. The lack of successful therapy for oral mucosal wounds has influenced clinicians to explore alternative treatments and potential autotherapies to enhance intraoral healing. ⋯ Studies were evaluated by injury models, therapy interventions, and outcome measures. The success of therapeutic approaches was assessed, and research outcomes were compared based on current hallmarks of oral wound healing. By leveraging therapeutic advancements, particularly within in cell-based biomaterials and immunoregulation, there is great potential for translational therapy in oral tissue regeneration.