Novel assay to detect damage caused to the iris by ocular antibiotics
28 Aug 2017
By Dr Subba Rao Gangi Setty, Senior Fellow
Indian Institute of Science, Bangalore
In our recently reported study in Experimental Eye Research, we show that application of antibiotics such as fluoroquinolones (FQLs) to the eye can cause toxicity in the iris melanocytes resulting in the release of melanin pigments into the aqueous humour. Additionally, we also developed an assay to measure these pigments which would hopefully improve our understanding of how these antibiotics cause toxicity.
Antibiotics such as FQLs are commonly used to treat eye infections but have also shown to be toxic. However, their effect on iris melanocyte (melanin-producing cells) pigmentation and phototoxicity has not been studied extensively in humans. Iris pigments contribute to the colour of the iris and are produced by melanin-synthesising enzyme called tyrosinase (TYR) present in melanocytes. Ocular antibiotics exposure results in iris melanocyte damage following accumulation of dispersed pigments, consisting of melanin deposits and melanocyte debris, in the aqueous humor of eye. These pigments can be visualized using slit-lamp biomicroscopy, but cannot be measured. Additionally, dispersed pigments have also been observed in eye diseases such as bilateral acute iris transillumination (BAIT) and bilateral acute depigmentation of iris (BADI), although the role of these class of antibiotics in developing these conditions is not fully understood.
In our published study, we proposed that dispersed pigments are possibly enriched with melanin-synthesizing enzyme tyrosinase and thus measuring the enzyme or its activity will directly correlate to the extent of melanocyte damage. We have developed a tyrosinase activity assay, which measures the amount of dispersed pigments in the aqueous humor of eye. Further, in collaboration with Narayana Nethralaya, Bangalore, we examined the iris depigmentation and TYR activity in the aqueous humor samples of 82 healthy eyes undergoing cataract surgery following topical application of FQLs.
Our experimental results suggest that antibiotics such as Ciprofloxacin and Moxifloxacin cause significant melanocyte toxicity. Additionally Moxifloxacin inhibited the tyrosinase activity at subclinical dose. Intriguingly, none of these patients developed any clinically significant ocular side effects characteristic of BAIT or BADI. Nevertheless, investigation of aqueous humor revealed that iris melanocytes produce “soluble tyrosinase” rather than cell membrane-bound tyrosinase which are found in all types of melanocytes. This unique soluble active tyrosinase forms a potential therapeutic target in cosmetic and skin lightning biology.
Aqueous humor tyrosinase activity is indicative of iris melanocyte toxicity. Mahanty, S., Kawali, A.A., Dakappa, S.S., Mahendradas, P., Kurian, M., Kharbanda, V., Shetty, R. and Setty, S.R. Experimental Eye Research (August 2017)