The doctoral dissertation in the field of Drug research will be examined at the Faculty of Health Sciences at Kuopio campus. The public examination will be streamed online.
What is the topic of your doctoral research? Why is it important to study the topic?
The eye is a complex organ with unique anatomical and physiological barriers. Therefore, a local drug administration to the eye is essential to gain therapeutic drug concentrations. In general, drug metabolism is a key determinant of the pharmacological and toxicological effects of drugs. However, there is little to no information on ocular drug metabolism. This work contributed to a systematic understanding of ocular carboxylesterases and aldehyde oxidase 1 activities and protein contents by analyzing multiple ocular tissues from humans, rabbits, and pigs. We hope this knowledge will aid in the development of improved ophthalmic drugs for which there is an increasing need due to rising incidence of ocular diseases in the aging populations.
What are the key findings or observations of your doctoral research?
We found significant variation in enzyme activities and protein expression levels in ocular tissues. Among esterases, carboxylesterase 1 appeared most prominent. Ocular aldehyde oxidase 1 exhibited highest levels in human eye tissues. Notable differences in enzyme inhibition patterns were observed for both enzyme activities. In vivo, results aligned well with in vitro data where rapid esterase-mediated hydrolysis of cefuroxime axetil was observed, while metabolism was slower but detectable for brimonidine, acetaminophen, and sunitinib.
How can the results of your doctoral research be utilised in practice?
The clear species and tissue differences in ocular activities and enzyme contents have highlighted the importance of determining enzyme profiles in each model species. This will further aid in understanding complications associated with translational studies. These novel findings on ocular drug-metabolizing enzymes should find use in the development of ocular therapeutics.
What are the key research methods and materials used in your doctoral research?
In this thesis work, we employed in vitro and in vivo methodologies to investigate ocular drug metabolism across species and ocular tissues. We assessed enzyme activities using optimized assays with human-selective probe substrates and validated them using both generic and isoform-selective inhibitors. For the first time, quantitative proteomic measurements of enzyme contents were done with mass spectrometry using isotope-labeled custom-designed peptides. Protein expression was confirmed with immunoblotting. To evaluate the extent of ocular drug metabolism in vivo, we administered a cocktail of drugs, which are substrates for multiple enzymes, via intracameral and intravitreal routes into rabbit eyes.
The doctoral dissertation of Anam Hammid, MSc, entitled Expression and activities of carboxylesterase and aldehyde oxidase inhuman, rabbit, and pig ocular tissues will be examined at the Faculty of Health Sciences at Kuopio campus. The Opponent in the public examination will be Professor Janne Backman of the University of Helsinki, and the Custos will be Professor Paavo Honkakoski of the University of Eastern Finland.
For further information, please contact:
Anam Hammid, MSc, anam.hammid(a)uef.fi, 0465354577
