Identification of Cell Types in Human Diseased Corneas

Kenney, M. Cristina; Chwa, Marilyn; Lin, Bingyi; Huang, Gang; Ljubimov, Alexander V.; Brown, Donald J.

doi:10.1097/00003226-200104000-00014

Cited by 26 publications

(17 citation statements)

References 20 publications

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“…As CD68 is expressed on macrophages and their precursors, monocytes, and is also present to a lesser extent on dendritic cells and peripheral blood granulocytes, those findings could be a suggestion of at least some degree of cellular infiltration with inflammatory cells in the keratoconic cornea, which would support the role of inflammation in keratoconus pathophysiology. 161 However, in contrast with that investigation, two studies did not find positive results for antibody markers for CD68 in keratoconus. 162, 163 Sykakis et al 164 reported in 2012 that they identified both isolated and aggregated nuclei at sites of Bowman's breaks in keratoconic corneas, for which the origin could not be identified (they did not look for the immunohistochemical expression of anti-CD68 antibody).…”

Section: Resultsmentioning

confidence: 65%

“…In addition, Kenney et al, 161 using immunohistochemistry, found that keratoconus corneas showed increased numbers of glycoprotein cluster of differentiation 68 (CD68)-positive cells within the stroma, and that the epithelial basement membrane in keratoconus corneas stained with that antibody. As CD68 is expressed on macrophages and their precursors, monocytes, and is also present to a lesser extent on dendritic cells and peripheral blood granulocytes, those findings could be a suggestion of at least some degree of cellular infiltration with inflammatory cells in the keratoconic cornea, which would support the role of inflammation in keratoconus pathophysiology.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Keratoconus: an inflammatory disorder?

Galvis

Sherwin

Tello

et al. 2015

Eye

302

199

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Keratoconus has been classically defined as a progressive, non-inflammatory condition, which produces a thinning and steepening of the cornea. Its pathophysiological mechanisms have been investigated for a long time. Both genetic and environmental factors have been associated with the disease. Recent studies have shown a significant role of proteolytic enzymes, cytokines, and free radicals; therefore, although keratoconus does not meet all the classic criteria for an inflammatory disease, the lack of inflammation has been questioned. The majority of studies in the tears of patients with keratoconus have found increased levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and matrix metalloproteinase (MMP)-9. Eye rubbing, a proven risk factor for keratoconus, has been also shown recently to increase the tear levels of MMP-13, IL-6, and TNF-α. In the tear fluid of patients with ocular rosacea, IL-1α and MMP-9 have been reported to be significantly elevated, and cases of inferior corneal thinning, resembling keratoconus, have been reported. We performed a literature review of published biochemical changes in keratoconus that would support that this could be, at least in part, an inflammatory condition.

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Section: Resultsmentioning

confidence: 65%

Section: Resultsmentioning

confidence: 99%

Keratoconus: an inflammatory disorder?

Galvis

Sherwin

Tello

et al. 2015

Eye

302

199

View full text Add to dashboard Cite

show abstract

“…For example, increased levels of cathepsins B, G, and V/L2 along with other lysosomal enzymes are found in KC corneas. 11,[47][48][49] Cathepsins can elevate hydrogen peroxide levels, thus increasing oxidative stress and apoptosis. 50 -54 KC corneas also have decreased levels of extracellular superoxide dismutase (EC-SOD, SOD3) activity 39 that may lead to higher levels of superoxides.…”

Section: Discussionmentioning

confidence: 99%

Increased Stress-Induced Generation of Reactive Oxygen Species and Apoptosis in Human Keratoconus Fibroblasts

Chwa

Atilano

Reddy

et al. 2006

Invest. Ophthalmol. Vis. Sci.

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140

124

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PURPOSE.To determine whether keratoconus (KC) corneal fibroblast cultures have increased reactive oxygen species (ROS) production and are more susceptible to stress-related challenges. METHODS. Normal (n ϭ 9) and KC (n ϭ 10) stromal fibroblast cultures were incubated in either neutral-or low-pH conditions, with or without hydrogen peroxide. Catalase activities were measured with a fluorescent substrate assay. Superoxide and ROS/reactive nitrogen species (RNS) productions were determined with an amine-reactive green-dye assay and 2Ј,7Ј-dichlorodihydrofluorescein diacetate (H 2 DCFDA) dye assay, respectively. Cell viability was analyzed by a dye-exclusion assay. Caspase 3 activity was measured by a fluorochrome inhibitor of caspase (FLICA) assay. A cationic (green) dye was used to measure the mitochondrial membrane potential (⌬⌿m). RESULTS. KC fibroblasts had increased superoxide and ROS/RNS production (6.2-fold, P Ͻ 0.001 and 1.8-fold, P Ͻ 0.001, respectively) and catalase activity (P Ͻ 0.01) with higher concentrations of H 2 O 2 compared with normal cultures (P ϭ 0.16). After a low-pH stress challenge, KC fibroblasts maintained higher ROS/RNS levels (3.3-fold, P Ͻ 0.02), showed higher caspase-3 activity (7.5-fold, P Ͻ 0.02) and decreased ⌬⌿m (2.6-fold, P Ͻ 0.04), and had decreased cell viability (37%, P Ͻ 0.005 vs. 20%, P Ͻ 0.27) compared with normal fibroblasts. CONCLUSIONS. Under identical conditions, KC fibroblasts had increased basal generation of ROS/RNS and were more susceptible to stressful challenges (low-pH and/or H 2 O 2 conditions) than were normal fibroblasts. In addition, the stressed KC fibroblasts possessed characteristics similar to those found in the intact KC corneas (increased catalase activity, ROS production, and apoptosis). These properties may play a role in the pathogenesis of KC. (Invest Ophthalmol Vis Sci.

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“…In keratoconus, stromal areas adjacent to regions where Bowman's layer was disrupted also stained for MDA. Because these regions are also associated with fibrosis (Kenney et al 1998(Kenney et al ,2000(Kenney et al ,2001, MDA staining may represent an association with fibrosis in the cornea.…”

Section: Malondialdehyde (Mda)mentioning

confidence: 99%

Evidence of Oxidative Stress in Human Corneal Diseases

Buddi

Lin

Atilano

et al. 2002

J Histochem Cytochem.

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325

229

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S U M M A R YThis study localized malondialdehyde (MDA, a toxic byproduct of lipid peroxidation), nitrotyrosine [NT, a cytotoxic byproduct of nitric oxide (NO)], and nitric oxide synthase isomers (NOS) in normal and diseased human corneas. Normal corneas ( n ϭ 11) and those with clinical and histopathological diagnoses of keratoconus ( n ϭ 26), bullous keratopathy ( n ϭ 17), and Fuchs' endothelial dystrophy ( n ϭ 12) were examined with antibodies specific for MDA, NT, eNOS (constitutive NOS), and iNOS (inducible NOS). Normal corneas showed little or no staining for MDA, NT, or iNOS, whereas eNOS was detected in the epithelium and endothelium. MDA was present in all disease groups, with each group displaying a distinct pattern of staining. NT was detected in all keratoconus and approximately one half of Fuchs' dystrophy corneas. iNOS and eNOS were evident in all the diseased corneas. Keratoconus corneas showed evidence of oxidative damage from cytotoxic byproducts generated by lipid peroxidation and the NO pathway. Bullous keratopathy corneas displayed byproducts of lipid peroxidation but not peroxynitrite (MDA but not NT). Conversely, Fuchs' dystrophy corneas displayed byproducts of peroxynitrite with little lipid peroxidation (NT ϾϾ MDA). These data suggest that oxidative damage occurs within each group of diseased corneas. However, each disease exhibits a distinctive profile, with only keratoconus showing prominent staining for both nitrotyrosine and MDA. These results suggest that keratoconus corneas do not process reactive oxygen species in a normal manner, which may play a major role in the pathogenesis of this disease.

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Identification of Cell Types in Human Diseased Corneas

Abstract: The current study demonstrates that increased presence of lysosomal enzymes, corneal remodeling, and fibrosis can occur in the absence of myofibroblasts and/or macrophages.

Cited by 26 publications

References 20 publications

Keratoconus: an inflammatory disorder?

Keratoconus: an inflammatory disorder?

Increased Stress-Induced Generation of Reactive Oxygen Species and Apoptosis in Human Keratoconus Fibroblasts

Evidence of Oxidative Stress in Human Corneal Diseases

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