Targeting Oxidative Stress and Inflammation in the Eye: Insights from a New Model of Experimental Autoimmune Uveitis.

Autoimmune uveitis is a relapsing blind-causing ocular condition with complex pathogenesis that is not completely understood. There is a high demand for accurate animal models of experimental autoimmune uveitis (EAU) suitable for elucidating the molecular mechanisms of the disease and testing new therapeutic approaches. Here, we demonstrated that photoreceptor Ca/Zn-sensor protein recoverin is a uveoretinal antigen in albino rabbits provoking typical autoimmune chorioretinitis 2-4 weeks after immunization.

Long-term humoral immunogenicity, safety and protective efficacy of inactivated vaccine against COVID-19 (CoviVac) in preclinical studies.

The unprecedented in recent history global COVID-19 pandemic urged the implementation of all existing vaccine platforms to ensure the availability of the vaccines against COVID-19 to every country in the world. Despite the multitude of high-quality papers describing clinical trials of different vaccine products, basic detailed data on general toxicity, reproductive toxicity, immunogenicity, protective efficacy and durability of immune response in animal models are scarce. Here, we developed a β-propiolactone-inactivated whole virion vaccine CoviVac and assessed its safety, protective efficacy, immunogenicity and stability of the immune response in rodents and non-human primates.

Conserved pan-cancer microenvironment subtypes predict response to immunotherapy.

The clinical use of molecular targeted therapy is rapidly evolving but has primarily focused on genomic alterations. Transcriptomic analysis offers an opportunity to dissect the complexity of tumors, including the tumor microenvironment (TME), a crucial mediator of cancer progression and therapeutic outcome. TME classification by transcriptomic analysis of >10,000 cancer patients identifies four distinct TME subtypes conserved across 20 different cancers.

Single-cell Spatial Proteomic Revelations on the Multiparametric MRI Heterogeneity of Clinically Significant Prostate Cancer.

Purpose: Multiparametric MRI (mpMRI) has become an indispensable radiographic tool in diagnosing prostate cancer. However, mpMRI fails to visualize approximately 15% of clinically significant prostate cancer (csPCa). The molecular, cellular, and spatial underpinnings of such radiographic heterogeneity in csPCa are unclear.

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

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.

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

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).

Light-Induced Thiol Oxidation of Recoverin Affects Rhodopsin Desensitization.

The excessive light illumination of mammalian retina is known to induce oxidative stress and photoreceptor cell death linked to progression of age-related macular degeneration. The photochemical damage of photoreceptors is suggested to occur via two apoptotic pathways that involve either excessive rhodopsin activation or constitutive phototransduction, depending on the light intensity. Both pathways are dramatically activated in the absence of rhodopsin desensitization by GRK1.

Mitochondria-targeted antioxidant SKQ1 protects cornea from oxidative damage induced by ultraviolet irradiation and mechanical injury.

Background: Cornea protects the eye against natural and anthropogenic ultraviolet (UV) damage and mechanical injury. Corneal incisions produced by UV lasers in ophthalmic surgeries are often complicated by oxidative stress and inflammation, which delay wound healing and result in vision deterioration. This study trialed a novel approach to prevention and treatment of iatrogenic corneal injuries using SkQ1, a mitochondria-targeted antioxidant approved for therapy of polyethiological dry eye disease.

Suppression of Light-Induced Oxidative Stress in the Retina by Mitochondria-Targeted Antioxidant.

Light-induced oxidation of lipids and proteins provokes retinal injuries and results in progression of degenerative retinal diseases, such as, for instance, iatrogenic photic maculopathies. Having accumulated over years retinal injuries contribute to development of age-related macular degeneration (AMD). Antioxidant treatment is regarded as a promising approach to protecting the retina from light damage and AMD.

Mitochondria-Targeted Antioxidant SkQ1 Prevents Anesthesia-Induced Dry Eye Syndrome.

Dry eye syndrome (DES) is an age-related condition increasingly detected in younger people of risk groups, including patients who underwent ocular surgery or long-term general anesthesia. Being a multifactorial disease, it is characterized by oxidative stress in the cornea and commonly complicated by ocular surface inflammation. Polyetiologic DES is responsive to SkQ1, a mitochondria-targeted antioxidant suppressing age-related changes in the ocular tissues.

The cancer-retina antigen recoverin as a potential biomarker for renal tumors.

The renal cell carcinoma is the ninth most common cancer with an increasing occurrence and mortality. Recoverin is the first retina-specific photoreceptor protein that was shown to undergo aberrant expression, due to its promoter demethylation, as a cancer-retina antigen in a number of malignant tumors. In this work, we demonstrated that recoverin is indeed expressed in 68.

Light-induced disulfide dimerization of recoverin under ex vivo and in vivo conditions.

Despite vast knowledge of the molecular mechanisms underlying photochemical damage of photoreceptors, linked to progression of age-related macular degeneration, information on specific protein targets of the light-induced oxidative stress is scarce. Here, we demonstrate that prolonged intense illumination (halogen bulb, 1500 lx, 1-5 h) of mammalian eyes under ex vivo (cow) or in vivo (rabbit) conditions induces disulfide dimerization of recoverin, a Ca(2+)-dependent inhibitor of rhodopsin kinase. Western blotting and mass spectrometry analysis of retinal extracts reveals illumination time-dependent accumulation of disulfide homodimers of recoverin and its higher order disulfide cross-linked species, including a minor fraction of mixed disulfides with intracellular proteins (tubulins, etc.