Pathogenesis of pterygia: role of cytokines, growth factors, and matrix metalloproteinases

Girolamo, Nick Di; Chui, Jeanie; Coroneo, Minas T.; Wakefield, Denis

doi:10.1016/j.preteyeres.2004.02.002

Cited by 288 publications

(302 citation statements)

References 258 publications

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“…Furthermore, MMP-9 protein was not detected after any of the treatments. It is conceivable that the expression of other MMPs was affected by this exposure, 6 however in the current study, no additional investigations were initiated to disclose them.…”

Section: Uvb-mediated Induction Of Mmp-1 Is Abrogated By Pd98059mentioning

confidence: 80%

“…However, these results should be interpreted with caution as different ocular surface epithelial cells can undergo phenotypic and functional changes under culture conditions. 6 Pterygia are tumor-like lesions that consist of a fibrovascular proliferative tissue mass (nonclonal in origin) that invade the cornea and are analogous to a rheumatoid synovial pannus. Although the human tissue specimens used in the current investigation do not clearly demonstrate basophilic elastotic degeneration, this is indeed a classical feature of pterygia (see figures within Di Girolamo and colleagues 9,12 ) that resemble the pathological changes found in photodamaged skin.…”

Section: Discussionmentioning

confidence: 99%

“…6,9,10,12 Conditioned media or total cell lysates from control, UVB-irradiated, growth factor-stimulated, or MAPK inhibitor-treated PECs were used as the antigenic source. Conditioned media [25 l plus 8 l of zymography sample buffer (see below)] or total cell lysates [25 l total volume (see sample preparation above) were electrophoretically separated on SDS-polyacrylamide gel electrophoresis (PAGE) using a 4% stacking and 10% resolving gels for MMP-1 (performed under nondenaturing conditions) or 12% resolving gel for ERK1/2 (performed under reducing conditions).…”

Section: Western Blottingmentioning

confidence: 99%

“…Proteins contained within the conditioned media or total cell lysates were transferred to PolyScreen polyvinylidene difluoride transfer membranes (Perkin-Elmer Life Sciences, Boston, MA) as previously described. 6,9,10,12 After transfer, the membranes were blocked in 5% skim milk powder in TBST for 1 hour, washed briefly in TBST, then probed with a predetermined concentration of primary antibody directed against human antigens (Table 1) diluted in 5% bovine serum albumin/TBST. Membranes were extensively washed in TBST (3 ϫ 5 minutes) and incubated with a 1:2000 dilution of the appropriate horseradish peroxidase-conjugated secondary antibody (Table 1) for 1 hour at room temperature.…”

Section: Western Blottingmentioning

confidence: 99%

“…[1][2][3][4][5] Despite this evidence, there is still controversy regarding the actual trigger for the development of pterygia and whether or not there is a genetic predisposition to this disease. 6 Recently, we have identified UVB as an environmental agent likely to be responsible for initiating molecular events that lead to the formation of pterygia. 7,8 From our hypothesis, 9 we postulate that UVB radiation activates cells at or near the limbus.…”

mentioning

confidence: 99%

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Epidermal Growth Factor Receptor Signaling Is Partially Responsible for the Increased Matrix Metalloproteinase-1 Expression in Ocular Epithelial Cells after UVB Radiation

Girolamo

Coroneo

Wakefield

2005

The American Journal of Pathology

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Pterygia are inflammatory, invasive, and proliferative lesions of the human ocular surface in which the matrix metalloproteinase (MMP) collagenase-1 (MMP-1) is highly expressed. Pterygia development may involve MMP-1 activity against interstitial fibrillar collagen, an abundant extracellular matrix component of the cornea, and its induction by ultraviolet light (UVB). We examined the pathways responsible for enhanced expression of MMP-1 in pterygium epithelial cells after UVB exposure and/or treatment with chemical inhibitors of mitogen-activated protein kinases or epidermal growth factor receptor. The induction of MMP-1 by UVB was comparable to that mediated by heparin-binding epidermal growth factor-like growth factor and epidermal growth factor. The epidermal growth factor receptor inhibitor PD153035 partially blocked the UVB-mediated induction of MMP-1 and totally abrogated its production after stimulation with either heparin-binding epidermal growth factor-like growth factor or epidermal growth factor. UVB exposure enhanced the phosphorylated form of ERK1/2 in a time-dependent manner whereas the ERK1/2 inhibitor PD98059 decreased this induction by at least fivefold. Transcripts for c-jun and c-fos were detected as early as 2 hours after UVB exposure and were suppressed by PD98059. The identification of a specific intracellular signaling pathway responsible for the enhanced production of a key enzyme that denatures intact fibrillar collagen has important implications for understanding the pathophysiology and future therapy for pterygia. Pterygium is a condition of the ocular surface characterized by squamous cell metaplasia and goblet cell hyperplasia. The lesion consists of a wing-shaped mass of fibrovascular conjunctival tissue that invades the normal cornea. Other obvious pathological changes include activation of stromal fibroblasts, a persistent inflammatory component, elastotic degeneration, and destruction of collagenous barriers such as Bowman's layer. Pterygia are particularly prevalent in heavily sun-exposed individuals in whom extensive epidemiological studies link this disease to excessive ultraviolet (UV) radiation. 1-5 Despite this evidence, there is still controversy regarding the actual trigger for the development of pterygia and whether or not there is a genetic predisposition to this disease. 6 Recently, we have identified UVB as an environmental agent likely to be responsible for initiating molecular events that lead to the formation of pterygia. 7,8 From our hypothesis, 9 we postulate that UVB radiation activates cells at or near the limbus. This activation may cause 1) phenotypic alterations in a distinct population of epithelial cells, 2) production of proinflammatory and angiogenic cytokines 7 and growth factors, 8 and 3) increased invasiveness due to enhanced production of matrix metalloproteinases (MMPs) over and above their natural tissue inhibitors (TIMPs). 6,9 -12 To date, we 6,9 -12 and others [13][14][15][16][17] have accumulated data from in vitro culture and in vivo tissue-b...

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Section: Uvb-mediated Induction Of Mmp-1 Is Abrogated By Pd98059mentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Western Blottingmentioning

confidence: 99%

Section: Western Blottingmentioning

confidence: 99%

mentioning

confidence: 99%

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Epidermal Growth Factor Receptor Signaling Is Partially Responsible for the Increased Matrix Metalloproteinase-1 Expression in Ocular Epithelial Cells after UVB Radiation

Girolamo

Coroneo

Wakefield

2005

The American Journal of Pathology

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Diffuse Keratoconjunctival Proliferation

Said

Mathew²,

Shaikh³

et al. 2008

Arch Ophthalmol

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Objective: To report a previously unrecognized benign bilateral widespread conjunctival and corneal proliferative condition with a potential to affect vision. Methods: A gradually progressive diffuse conjunctival proliferation extending on the cornea was noted in 14 patients (28 eyes). These patients were followed up for a mean of 6 years for the site, extent, and progression of the condition. Six eyes had these lesions removed and studied histopathologically. Results: Patients included 6 men and 8 women (mean age, 57 years). Two patients had bilateral nasal lesions only, 1 patient had bilateral temporal lesions only, 6 patients had both nasal and temporal lesions, and 5 patients had lesions that extended circumferentially. Pathology reports showed dense collagenous tissue, a

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Linc‐9432 is a novel pterygium lincRNA which regulates differentiation of fibroblasts

et al. 2018

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Long intergenic noncoding RNAs (lincRNAs) are not fully characterized in disease, although many are involved in controlling differentiation. We discovered and sequenced a novel 4.4 kb human lincRNA called linc-9432 in pterygium, an ocular disease characterized by a wedge lesion. This transcript inhibited differentiation-induced cell death, promoted expression of stem cell markers, and decreased expression of epithelial and mesenchymal differentiation markers. This lincRNA regulated 30 differentiation-related genes in transcriptome analysis and 17/30 gene products were known to be directly associated in a network. When the lincRNA was silenced with pooled siRNA, the levels of these transcripts decreased in accordance with their predicted binding affinity for the lincRNA. TBC1D8B had the strongest affinity, interacting in-vitro at positions 269-292 within TBC1D8B.

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Pathogenesis of pterygia: role of cytokines, growth factors, and matrix metalloproteinases

Cited by 288 publications

References 258 publications

Epidermal Growth Factor Receptor Signaling Is Partially Responsible for the Increased Matrix Metalloproteinase-1 Expression in Ocular Epithelial Cells after UVB Radiation

Epidermal Growth Factor Receptor Signaling Is Partially Responsible for the Increased Matrix Metalloproteinase-1 Expression in Ocular Epithelial Cells after UVB Radiation

Diffuse Keratoconjunctival Proliferation

Linc‐9432 is a novel pterygium lincRNA which regulates differentiation of fibroblasts

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