Therapeutic Proteins for Treatment of Corneal Epithelial Defects

Abstract

Corneal epithelial disorders take pride of place in modern ophthalmology. Defects of corneal epithelium are commonly accompanied by blurry vision, photophobia and tearing. Since cornea is the most densely innervated tissue of organisms, its disruption leads to development of a severe pain syndrome. Mild corneal erosions commonly undergo quick spontaneous recovery. Suppression of corneal wound healing due to various pathological causes results in development of severe recurrent erosions and persistent corneal defects. These pathological events can in turn lead to corneal scarring, opacification, and ulceration of cornea, and ultimately to the permanent vision impairment. The etiology of the underlying corneal diseases that commonly involves inflammatory, neurotrophic and systemic factors, should be considered for treating such defects. Therefore, the research focus has been shifted to establish therapeutics based on proteins and peptides. Due to varied mechanisms of action, proteinbased pharmaceuticals can be involved in the protection of corneal surface, mimicking tear components, stimulation of corneal wound healing, regeneration of corneal innervation, suppressing oxidative stress, inflammation and neovascularization. The active components can be naturally occurring (blood- or tear-derived) or be created de novo and optimized in order to achieve the level of activity required. Such pharmaceuticals are characterized by low toxicity and absence of systemic side-effects due to their low absorption into the bloodstream, if administrated topically. This review summarizes existing data on protein-based drugs for treatment of corneal epithelial defects that are currently under preclinical development or testing in clinical trials, or approved for medical use.

Mitochondria‐Targeted Antioxidant SkQ1 Prevents Anesthesia‐Induced Dry Eye Syndrome

“…It is widely regarded that DES pathogenesis involves inflammatory component [ 9 , 39 ]. The oxidative stress of the cornea detected in our DES model can induce inflammatory responses of the ocular surface tissues [ 41 ] that may be sensitive to SkQ1 action.…”

“…Yet, such medications are generally based on cytokines, growth factors, hormones, and other naturally occurring tear components and, as such, could produce multifaceted and often contradictory effects on the corneal homeostasis. In addition, the majority of protein-based medications are not yet approved for clinical use [ 9 ]. All things considered, the demand for novel approaches to treating DES remains a highly relevant problem in current ophthalmology.…”

Inflammation in Dry Eye Syndrome: Identification and Targeting of Oxylipin-Mediated Mechanisms

“…The most critical consequences of this desiccating stress are ocular surface inflammation and damage, which in severe cases can cause blindness, due to corneal scarring, opacification or ulceration [3]. Consistently, the generally accepted treatment of DES involves not only using lubricating eye drops and ointments, but also topical anti-inflammatory therapy [9,10]. Unfortunately, the administration of common ocular anti-inflammatory medications, such as corticosteroid eye drops or cyclosporine, is associated with a number of adverse effects in patients with dry eye, which generally limits their employment [11].…”

Inflammatory metabolites of arahidonic acid in tear fluid in UV-induced corneal damage

“…Ключевые слова: УФ-индуцируемые повреждения роговицы; апоптоз кератоцитов; кератит; слезная плёнка; эйкозаноиды; простагландин Е 2 ; простагландин D 2 ; 15d-PGJ 2 ; 5-HETE; 12-HETE DOI: 10.18097/PBMC20196501033 * -адресат для переписки Благодаря присутствию в роговице соответствующих фотосенсибилизаторов, УФ-свет является непосредственным триггером повреждения этой ткани [5][6][7]. Так, облучение запускает сигнальный ответ клеток (так называемый УФ-ответ), включающий экспрессию специализированных генов.…”

“…Однако не менее важную роль в развитии повреждений роговицы и затруднении её регенерации играют локальные воспалительные процессы. В норме острый воспалительный ответ в роговице подавлен за счёт отсутствия антиген-презентирующих клеток и кровеносных сосудов, а также содержания ряда иммуносупрессорных агентов [7]. Однако УФ-облучение стимулирует накопление провоспалительных цитокинов в клетках эпителия роговицы [6], что создает цитотоксичную среду, нарушает упорядоченность слоев роговицы, замедляет регенеративные процессы и повышает вероятность её рубцевания и неоваскуляризации [7].…”