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Victor M. Bautista, Sr., Marilú Arredondo-Flores, Nadia Luz López-Espinosa, Teresa Valdéz-González, Herlinda Mejía-López; Doxycycline'S Effect In Primary Pterygium Proteome Apoptosis. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5129.
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© ARVO (1962-2015); The Authors (2016-present)
Pterygium is a benign and fibrovascular lesion, originated from the bulbar conjunctiva. In pterygium has been described abnormal expression of apoptotic genes. We recently described that apoptosis is inhibited by the overexpression of peroxiredoxin 2 and anti-apoptotic proteins like Hsp-70, that block cytochrome c release and caspase activation, it results in a pro-caspase 3 accumulation. Some reports showed that doxycycline has pro-apoptotic effects activating caspase 3, 7 and 9, and inhibiting matrix metalloproteinase activity, and inducing cytochrome c release into cytosol. The aim of this work was to analyze in vivo the effect of doxycycline in pterygium proteome apoptosis
Eigth patients with primary pterygia, previous informed consent, were treated with topic 2% doxycycline during two weeks and eigth no treated patients with primary pterygia and were analyzed by apoptosis protein array. Pterygia were rejected by surgery and were lysed. Two-hundred micrograms of proteins were incubated with the arrays and revealed with chemoluminiscence and spots density was quantified in G-BOX system. Fold change between pterygium treated and non-treated was obtained in order to establish relative protein expression. This study was approved by Scientific and Ethics Committees of Hospital "Nuestra Señora de la Luz" at Mexico City.
The analyzed results showed that in doxycycline treated pterygia 9 proteins were overexpressed, 2 proteins not had changes and 24 were down-expressed. Only catalase showed a fold change more than 2 times. Interestingly procaspase 3, clusterin, cytochrome c, Fas/TNFRSF6, HIF-1a, SMAC/DIABLO and caspase 3 were down expressed in comparison to previously report where we describe that these proteins were overexpressed in primary pterygium (ARVO 2011). The expression of bcl-2 and bcl-x decreased in doxycycline treated pterygia.
We have described apoptosis inhibition in pterygium by overexpression of anti-apoptotic proteins and also reported the effect in vitro of doxycycline in pterygia cells, where doxycycline reduced cell viability and induced the production of TNF-alpha an others cytokines. In this work we describe the down expression of several apoptotic proteins by doxycycline's effect that suggest that apoptosis pathway in pterygium is recovered in contrast to apoptotic proteome described previously. Doxycycline could be an important part in the treatment of pterygium.
Clinical Trial: :
Ethics Committee of Hospital "Nuestra Señora de la Luz", None
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