Abnormal distribution of trace elements in keratoconic corneas

Sé, Avetisov; Vr, Mamikonyan; Ia, Novikov; Pateyuk, L.S.; Osipyan, GA; Np, Kiryushchenkova

doi:10.17116/oftalma2015131634-42

Cited by 12 publications

(6 citation statements)

References 25 publications

(22 reference statements)

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“…response are observed in Hmox1 knock-out mice [42]. Interestingly iron accumulation is frequently observed in KC corneas [43]. Moreover, HMOX1 promoter also contains an AP1 response element, which is the other pathway used to activate this enzyme.…”

Section: Plos Onementioning

confidence: 99%

Corneal epithelium in keratoconus underexpresses active NRF2 and a subset of oxidative stress-related genes

et al. 2022

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Keratoconus (KC) is a multifactorial progressive ectatic disorder characterized by local thinning of the cornea, leading to decreased visual acuity due to irregular astigmatism and opacities. Despite the evolution of advanced imaging methods, the exact etiology of KC remains unknown. Our aim was to investigate the involvement of corneal epithelium in the pathophysiology of the disease. Corneal epithelial samples were collected from 23 controls and from 2 cohorts of patients with KC: 22 undergoing corneal crosslinking (early KC) and 6 patients before penetrating keratoplasty (advanced KC). The expression of genes involved in the epidermal terminal differentiation program and of the oxidative stress pathway was assessed by real time PCR analysis. Presence of some of the differentially expressed transcripts was confirmed at protein level using immunofluorescence on controls and advanced KC additional corneal samples. We found statistically significant under-expression in early KC samples of some genes known to be involved in the mechanical resistance of the epidermis (KRT16, KRT14, SPRR1A, SPRR2A, SPRR3, TGM1 and TGM5) and in oxidative stress pathways (NRF2, HMOX1 and HMOX2), as compared to controls. In advanced KC samples, expression of SPRR2A and HMOX1 was reduced. Decreased expression of keratin (KRT)16 and KRT14 proteins was observed. Moreover, differential localization was noted for involucrin, another protein involved in the epidermis mechanical properties. Finally, we observed an immunofluorescence staining for the active form of NRF2 in control epithelia that was reduced in KC epithelia. These results suggest a defect in the mechanical resistance and the oxidative stress defense possibly mediated via the NRF2 pathway in the corneal keratoconic epithelium.

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Section: Plos Onementioning

confidence: 99%

Corneal epithelium in keratoconus underexpresses active NRF2 and a subset of oxidative stress-related genes

et al. 2022

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“…При гистологическом исследовании качественной химической реакцией с «берлинской лазурью» было доказано присутствие железа в базальных клетках эпителия в зоне пигментного кольца [39]. Современными методами аналитической химии (рентгенофлуоресцентный анализ и энергодисперсионная рентгеновская спектроскопия на базе сканирующего электронного микроскопа) было определено накопление меди, железа и цинка (элементы халькофильной группы) в зоне кольца Флейшера (в поверхностных слоях стромы, в области боуменовой мембраны и в эпителии роговицы), что послужило основой для новой концепции патогенеза КК [40]. Согласно современным представлениям, причиной деструктивных изменений в тканях роговицы при этом заболевании является минеральный дисметаболизм с аномальным перераспределением химических элементов.…”

Section: описание клинического наблюденияunclassified

Fleischer Ring in "Subclinical" Keratoconus (Clinical Case)

Патеюк¹

2023

Офтальмология. Восточная Европа

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Кератоконус (КК) – эктатическое заболевание роговицы, клинически проявляющееся постепенным увеличением силы неправильного роговичного астигматизма с прогрессирующим снижением зрительных функций. Диагностика этого заболевания на развитых стадиях с типичной клинической картиной, как правило, не представляет затруднений. Сложности в офтальмологической практике возникают в нетипичных случаях КК с непрогрессирующим течением и/или в случаях КК на самых начальных стадиях его развития. Возросшая в настоящее время актуальность верификации диагноза на самых начальных стадиях заболевания в первую очередь обусловлена рисками прогрессирования кератэктазии после кераторефракционных вмешательств в случаях недиагностированного КК. В некоторой степени диагностику осложняет существующая терминологическая неопределенность ввиду отсутствия однозначного трактования таких понятий, как «субклиническая стадия КК», «латентный КК», «forme fruste КК», «подозрение на КК» и др. Под нашим наблюдением находился пациент Д. 23 лет, обратившийся с целью предоперационного обследования на предмет возможности проведения эксимерлазерной коррекции зрения. В результате офтальмологического обследования был поставлен диагноз «кератоконус обоих глаз»: развитой на правом глазу и начальный на левом. Особенность клинической картины заключается, во-первых, в отсутствии прогрессирующего течения заболевания на обоих глазах, а во-вторых, в отсутствии патологических кератотопографических изменений на левом глазу при наличии патогномоничного для КК биомикроскопического признака – кольца Флейшера. Приведенный в настоящей статье клинический случай наличия кольца Флейшера в отсутствие кератотопографических отклонений объясним с позиции современной концепции патогенеза КК, согласно которой протрузия роговицы возникает вследствие деструктивных изменений в соединительнотканной строме, вызванных нарушением метаболизма минеральных элементов халькофильной группы – меди, цинка и железа. Примечателен факт того, что нарушение минерального обмена в роговице проявляется в виде кольца Флейшера уже на самой начальной стадии КК – на этапе ультра- и микроструктурных изменений, еще до развития кератотопографических отклонений. Keratoconus (KC) is an ectatic disorder of the cornea, characterized by gradually increasing irregular corneal astigmatism with a progressive visual impairment. Diagnosis at advanced stages of the disease with typical clinical manifestations is a matter of routine. Nevertheless, recognition of unusual cases of KC with a non-progressive course and/or at the initial stages is still a challenge in ophthalmological practice. Nowadays early KC precise diagnosis is highly relevant due to considerable risks of keratectasia progression after keratorefractive surgery performed in cases of undiagnosed disease. The diagnostic approach is some kind complicated by the terminological confusion since the uncertain interpretation of such terms as "subclinical stage of KC", "latent KC", "forme fruste KC", "KC suspect", etc. exists. Here in the article we present a clinical observation of 23 years old male patient, who underwent pre op screening for excimer laser surgery. Ophthalmologic examination revealed KC in both eyes: moderate/advanced stage on the right eye, and early/mild stage on the left eye. This clinical case singularity is that the disease didn’t progress in both eyes, and that the left one showed no corneal topographic abnormalities, but exhibited Fleischer ring – KC pathognomonic slit-lamp sign. The presence of Fleischer ring in the absence of corneal topographic abnormalities in the described clinical case could be explained within the modern concept of KC pathogenesis, which states that corneal protrusion occurs due to destructive changes in the corneal stroma connective tissue, resulted from chalcophile minerals (copper, zinc and iron) dismetabolism. It is noteworthy that mineral metabolism impairment manifests itself in the form of a Fleischer ring at the very initial stage of KC – stage of ultra- and microstructural changes, prior to corneal topographic abnormalities.

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“…This would inhibit transfer of Cu ions to the center of the cornea [62], thus generating a localized deficit of Cu. In this vein, peripheral Cu deposition is a common clinical feature in KC patients (i.e., Fleischer ring) [62][63][64]. The mechanism(s) through which deficiency of metal ions may promote KC formation are manifold.…”

Section: Mineralsmentioning

confidence: 99%

“…Dysregulated iron metabolism has also been hypothesized in KC corneas. In fact, Fe has been detected, together with Cu, in the corneal Fleischer ring [62,63]. Due to Fe peripheral deposition, it was hypothesized that central unavailability of Fe contributes to KC development, because it works as a cofactor of lysyl hydroxylase (LH), which is required for the collagen crosslinking process.…”

Section: Mineralsmentioning

confidence: 99%

Nutritional and Metabolic Imbalance in Keratoconus

et al. 2022

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Keratoconus (KC) is a progressive corneal degeneration characterized by structural changes consisting of progressive thinning and steepening of the cornea. These alterations result in biomechanical weakening and, clinically, in vision loss. While the etiology of KC has been the object of study for over a century, no single agent has been found. Recent reviews suggest that KC is a multifactorial disease that is associated with a wide variety of genetic and environmental factors. While KC is typically considered a disease of the cornea, associations with systemic conditions have been well described over the years. In particular, nutritional and metabolic imbalance, such as the redox status, hormones, metabolites, and micronutrients (vitamins and metal ions), can deeply influence KC initiation and progression. In this paper, we comprehensively review the different nutritional (vitamins and minerals) and metabolic (hormones and metabolites) factors that are altered in KC, discussing their possible implication in the pathophysiology of the disease.

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Abnormal distribution of trace elements in keratoconic corneas

Cited by 12 publications

References 25 publications

Corneal epithelium in keratoconus underexpresses active NRF2 and a subset of oxidative stress-related genes

Corneal epithelium in keratoconus underexpresses active NRF2 and a subset of oxidative stress-related genes

Fleischer Ring in "Subclinical" Keratoconus (Clinical Case)

Nutritional and Metabolic Imbalance in Keratoconus

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