Iatrogenic Damage of Eye Tissues: Current Problems and Possible Solutions

Baksheeva, Viktoriia E.; Gancharova, Olga; Tiulina, Veronika V.; Iomdina, Elena N.; Zamyatnin, Andrey A.; Philippov, Pavel P.; Zernii, Evgeni Yu; Senin, Ivan I.

doi:10.1134/s0006297918120143

Cited by 6 publications

(2 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Being conveniently simulated in animals, LIRD models are commonly employed for studies of pathogenesis and trailing of therapeutic approaches with respect to these diseases [9]. Spontaneous photochemical damage to the retina can be induced, for instance, by intensive light exposure from ophthalmological illuminators [10][11][12]. As an aggravating factor, excessive light illumination of the retina contributes to AMD and other retinal degenerative disorders by inducing the apoptosis of photoreceptors and other pathological hallmarks [8,13].…”

Section: Introductionmentioning

confidence: 99%

Mechanisms and Treatment of Light-Induced Retinal Degeneration-Associated Inflammation: Insights from Biochemical Profiling of the Aqueous Humor

Chistyakov

Baksheeva

Tiulina

et al. 2020

IJMS

View full text Add to dashboard Cite

Ocular inflammation contributes to the pathogenesis of blind-causing retinal degenerative diseases, such as age-related macular degeneration (AMD) or photic maculopathy. Here, we report on inflammatory mechanisms that are associated with retinal degeneration induced by bright visible light, which were revealed while using a rabbit model. Histologically and electrophysiologically noticeable degeneration of the retina is preceded and accompanied by oxidative stress and inflammation, as evidenced by granulocyte infiltration and edema in this tissue, as well as the upregulation of total protein, pro-inflammatory cytokines, and oxidative stress markers in aqueous humor (AH). Consistently, quantitative lipidomic studies of AH elucidated increase in the concentration of arachidonic (AA) and docosahexaenoic (DHA) acids and lyso-platelet activating factor (lyso-PAF), together with pronounced oxidative and inflammatory alterations in content of lipid mediators oxylipins. These alterations include long-term elevation of prostaglandins, which are synthesized from AA via cyclooxygenase-dependent pathways, as well as a short burst of linoleic acid derivatives that can be produced by both enzymatic and non-enzymatic free radical-dependent mechanisms. The upregulation of all oxylipins is inhibited by the premedication of the eyes while using mitochondria-targeted antioxidant SkQ1, whereas the accumulation of prostaglandins and lyso-PAF can be specifically suppressed by topical treatment with cyclooxygenase inhibitor Nepafenac. Interestingly, the most prominent antioxidant and anti-inflammatory benefits and overall retinal protective effects are achieved by simultaneous administrating of both drugs indicating their synergistic action. Taken together, these findings provide a rationale for using a combination of mitochondria-targeted antioxidant and cyclooxygenase inhibitor for the treatment of inflammatory components of retinal degenerative diseases.

show abstract

Section: Introductionmentioning

confidence: 99%

Mechanisms and Treatment of Light-Induced Retinal Degeneration-Associated Inflammation: Insights from Biochemical Profiling of the Aqueous Humor

Chistyakov

Baksheeva

Tiulina

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…DES affects up to 40% of the adult population and manifests as eye irritation, hyperemia, glare, eye fatigue, and blurred vision [2,3]. Etiologically, alterations in tear homeostasis are associated with dysfunction of the lachrymal and/or Meibomian glands (such as in Sjögren syndrome and Meibomian Gland Dysfunction (MGD)) as well as a number of other factors, including contact lens wearing, adverse effects of various medications, complications of ocular surgery and general anesthesia [1,[4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

View full text Add to dashboard Cite

Dry eye syndrome (DES) is characterized by decreased tear production and stability, leading to desiccating stress, inflammation and corneal damage. DES treatment may involve targeting the contributing inflammatory pathways mediated by polyunsaturated fatty acids and their derivatives, oxylipins. Here, using an animal model of general anesthesia-induced DES, we addressed these pathways by characterizing inflammatory changes in tear lipidome, in correlation with pathophysiological and biochemical signs of the disease. The decline in tear production was associated with the infiltration of inflammatory cells in the corneal stroma, which manifested one to three days after anesthesia, accompanied by changes in tear antioxidants and cytokines, resulting in persistent damage to the corneal epithelium. The inflammatory response manifested in the tear fluid as a short-term increase in linoleic and alpha-linolenic acid-derived oxylipins, followed by elevation in arachidonic acid and its derivatives, leukotriene B4 (5-lipoxigenase product), 12-hydroxyeicosatetraenoic acid (12-lipoxigeanse product) and prostaglandins, D2, E2 and F2α (cyclooxygenase products) that was observed for up to 7 days. Given these data, DES was treated by a novel ophthalmic formulation containing a dimethyl sulfoxide-based solution of zileuton, an inhibitor of 5-lipoxigenase and arachidonic acid release. The therapy markedly improved the corneal state in DES by attenuating cytokine- and oxylipin-mediated inflammatory responses, without affecting tear production rates. Interestingly, the high efficacy of the proposed therapy resulted from the synergetic action of its components, namely, the general healing activity of dimethyl sulfoxide, suppressing prostaglandins and the more specific effect of zileuton, downregulating leukotriene B4 (inhibition of T-cell recruitment), as well as upregulating docosahexaenoic acid (activation of resolution pathways).

show abstract

Surgical and Nonsurgical Trauma

Yanoff,

Sassani

2025

Ocular Pathology

View full text Add to dashboard Cite

Iatrogenic Damage of Eye Tissues: Current Problems and Possible Solutions

Cited by 6 publications

References 91 publications

Mechanisms and Treatment of Light-Induced Retinal Degeneration-Associated Inflammation: Insights from Biochemical Profiling of the Aqueous Humor

Mechanisms and Treatment of Light-Induced Retinal Degeneration-Associated Inflammation: Insights from Biochemical Profiling of the Aqueous Humor

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

Surgical and Nonsurgical Trauma

Contact Info

Product

Resources

About