Abstract
BackgroundThe purpose of this research is to compare the histological and immunohistochemical changes induced by fixed combinations of timolol maleate and prostaglandin analogues in the rabbit conjunctiva. Thirty left eyes of rabbits, divided into three groups, were treated for 30 days with the following combinations of drugs: bimatoprost 0.03% + timolol 0.5%, travoprost 0.004% + timolol 0.5% and latanoprost 0.005 + timolol 0.5%. The right eyes served as controls and received no medication. At the end of the experiment, after enucleation, the conjunctivas were assessed through histomorphometry (number of inflammatory and goblet cells, epithelial thickness) and immunohistochemistry (anti-actin antibody to assess the degree of fibrosis).ResultsHistomorphometrically, there was infiltration of inflammatory cells in all the treated eyes. An increased number of goblet cells was observed with the use of all fixed combinations of prostaglandin analogues associated with timolol maleate in comparison with the control group. The combination travoprost + timolol resulted in more intense fibrosis. The effect of bimatoprost + timolol caused an intermediate reaction pattern among the other drugs, fostering higher numbers of goblet cells in the conjunctival epithelium, more than the other fixed combinations in this study. There was a difference in the comparison of goblet cells of eyes treated with bimatoprost + timolol (16.11 ± 2.42) and of those treated with latanoprost + timolol (13.18 ± 1.60) (P = 0.016).ConclusionIt was found that all fixed combinations of prostaglandins analogues + timolol induce a reaction in the conjunctiva, increasing the inflammatory infiltrate.
Highlights
The purpose of this research is to compare the histological and immunohistochemical changes induced by fixed combinations of timolol maleate and prostaglandin analogues in the rabbit conjunctiva
An increase was observed in the number of conjunctival inflammatory cells in all groups when compared to the control eyes
This increase was more intense in the group treated with latanoprost + timolol (19.44 ± 2.83 to 26.55 ± 4.75; P = 0.0004), followed by the group treated with travoprost + timolol (18.74 ± 2.08 to 23.88 ± 3.94; P = 0.0032) and that treated with bimatoprost + timolol (19.56 ± 1.97 to 22.24 ± 3.02; P = 0.0305) (Graphic 1 in Additional file 1; Figure 2)
Summary
The purpose of this research is to compare the histological and immunohistochemical changes induced by fixed combinations of timolol maleate and prostaglandin analogues in the rabbit conjunctiva. Some studies have shown that the main topical medications used to treat glaucoma increase the number of fibroblasts and inflammatory cells in the conjunctival substantia propria and induce epithelial metaplasia, causing changes in its structure. Lymphocytes, mast cells and fibroblasts, in addition to the reduction of goblet cell density, were reported in the conjunctiva in patients having chronic treatment with beta blockers [13] These cellular changes can cause tear film instability, leaving the cornea and conjunctiva more exposed to external agents [14]. This study aimed to evaluate the structural and inflammatory changes induced by fixed combinations of prostaglandin analogues (latanoprost, travoprost and bimatoprost) and timolol maleate
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