Throughout the year, Department of Ophthalmology faculty members welcome medical student involvement in research projects. Medical students interested in pursuing research in the Department of Ophthalmology should review the topics below and contact the faculty member directly.
Identification of the subcellular localization of wild-type and mutant fibulin-3
Mentor: John D. Hulleman, Ph.D.
The rare retinal dystrophy, Malattia Leventinese, is caused by a mutation of an arginine residue at the 345th position in a protein called fibulin-3. Instead of incorporating an arginine residue, a change in the DNA code results in the insertion of a large, bulky tryptophan residue, thus the mutation is called Arg345Trp (R345W). This mutation site occurs in a specific region of the protein called an epidermal growth factor (EGF) domain.
The presence of this large tryptophan residue causes problems with fibulin-3 protein folding and its eventual secretion from cells. As a result, the disease-causing mutant protein is poorly secreted and has a tendency to activate the cell’s stress responsive signaling pathways.
In healthy individuals, misfolded proteins are normally recognized by the cellular quality control machinery and targeted for degradation, effectively removing them from the cell. However, an interesting aspect of this R345W mutation is that it is not effectively degraded within the cell. This observation begs the question: Where is mutant fibulin-3 located within the cell the renders it resistant to degradation? Is it localized in vesicles? Is it trapped in the Golgi apparatus? Can we identify ways to target mutant, disease-causing fibulin-3 for degradation?
The overall goal of this project is to determine the intracellular localization of wild-type (normal) and R345W (mutant) fibulin-3 in human retinal pigmented epithelial cells.
The student who undertakes this study will develop a skill set enriched in molecular biology and cell biology techniques including: aseptic cell culturing, mammalian cell transduction, immunohistochemistry, epifluorescence microscopy, and confocal microscopy.
Generation of high-throughput-capable fusion proteins for identifying new drugs to treat retinal diseases
Mentor: John D. Hulleman, Ph.D.
A number of retinal disorders are caused by genetic mutations in genes encoding for secreted proteins. Many of these mutations compromise protein folding, and thus cause a defect in the protein’s secretion efficiency. Identifying compounds which rescue the mutant protein’s secretion defect is of substantial interest to my lab. However, since a cell at any given time secretes tens of thousands of proteins, it is difficult to specifically monitor the secretion of the one protein.
Researchers have therefore developed reporter assays to follow a single protein by modifying it and making it unique compared to the rest of the cell’s proteome. One such reporter assay strategy is to fuse is a light-generating enzyme (luciferase) to the protein of interest. Then, using an assay to detect the amount light given off in a sample, researchers can infer how much protein of interest is present. Such an approach can be useful for identifying new potential drugs which rescue the secretion defects using unbiased screening techniques in a high-throughput manner.
The goal of this project will be to use the Gaussia luciferase or Nano luciferase as a way to follow the secretion of retinal disease-associated proteins. Following the successful establishment and validation of this assay, the student will perform small-scale high-throughput screening experiments to identify drugs which may rescue the secretion of the mutant protein.
The student who is assigned to this project will develop skills associated with molecular biology, cell biology, and high-throughput screening. Specifically, s/he will be taught molecular cloning, luciferase assay development, cell culture, high-throughput screening, secondary assay verification, and quantitative PCR.
Positive and negative predictive values of topical steroid response for glaucoma induced by depot steroids
Mentor: Chan Nguyen, M.D., Ph.D.
Intravitreal and sub-Tenon’s steroid injections are useful for a number of ocular conditions including edema from diabetic retinopathy and retinal vein occlusions. However, use of these depot injections is hampered by the fear of inducing intractable glaucoma by steroid that cannot be removed once given. In contrast, the glaucoma induced by topical steroids is generally reversible once the drops are stopped. Although usually not useful as a treatment for posterior segment disease, topical steroids may serve as a useful test by which steroid-responsive individuals can be identified.
The goal of this retrospective study is to determine the positive and negative predictive values of topical steroid response for glaucoma induced by depot steroids. The patient population will include patients who were prescribed a course of topical steroids after pterygium excision and who subsequently underwent depot steroid injections for macular edema related to diabetes or retinal vein occlusion.
Driving practices of visually impaired patients in a large county hospital eye clinic
Mentor: Chan Nguyen, M.D., Ph.D.
Most states have laws requiring physicians to report patients with seizures to the Department of Motor Vehicles. However, no such laws exist for visually impaired patients. In this prospective questionnaire-based IRB-approved study, Parkland patients not meeting the Texas vision standard for an unrestricted driver’s license will be questioned about their driving habits and license status. This will help determine the potential scope of the problem of unreported visually impaired drivers.
Second- and third-year ophthalmology residents are required to complete a research project, to be presented at the Annual Resident and Alumni Day on Saturday, June 11, 2016.
Medical students are invited to assist the residents with their projects listed below:
Christopher Lee, M.D. (PGY4)
Project: This project will look at the effect of anti-VEGF intravitreal injections on intraocular pressure (Avastin, Eylea, and Lucentis). Specifically, I am interested in how these intravitreal injections affect patients who have a diagnosis of glaucoma and whether or not multiple rounds of injections cause an elevation in intraocular pressure leading to worsening of glaucoma.
Responsibilities: Assist in a retrospective chart review of patients who received anti-VEGF intravitreal injections in the UTSW faculty Aston Clinic from 2012–2015. The medical student will examine the medical records and create a document (chart) that includes patients’ intraocular pressure, vision, number of injections, and type of medication injected for each patient. This data will then be statistically analyzed to look at the trend of intraocular pressure over time as patients receive these injections.
Faculty Advisor: Jess T. Whitson, M.D.
Lilian Nguyen, M.D. (PGY2)
Project: This project will examine various outcomes after implementing diabetic teleretina screening in a low-income inner-city population. Diabetic retinopathy is the leading cause of blindness among adults aged 20–64 years in the United States, so there needs to be an effective and efficient method of screening; that is what this project aims to investigate.
The study design will be a retrospective chart review of all patients who underwent diabetic teleretina screening within the Parkland Health & Hospital System. Medical records of these patients will be identified. From these records, we will investigate the red (proliferative diabetic retinopathy or diabetic macular edema) ophthalmology referrals to see the cause for referral and whether the exam verified findings as well as compliance with follow-up.
We will investigate the yellow referrals to optometry (unreadable, or with mild/moderate non-proliferative diabetic retinopathy or some other finding) to see the cause for referral and whether the exam verified findings and how many were sent due to an unreadable image.
We will also investigate the green reads, which are ones without retinopathy, and see if they were eventually seen by an optometrist or an ophthalmologist for a different reason, if the initial read was in fact correct, or if they did have some degree of diabetic retinopathy.
Overall we will be looking at the numbers screened, the efficacy of photography for determining pathology, and costs.
Responsibilities: The medical student's main responsibilities will be assisting the resident with chart review. If they would like, they can also assist with writing up the project, but that is not necessary. They can really be as much or as little involved as they want – any help is appreciated! And of course their name would be on the project.
Faculty Advisor: Preston H. Blomquist, M.D.
Will Waldrop, M.D. (PGY3)
Project: Corneal changes after endothelial corneal transplant. This is a really exciting project with a high probability of publishing if we can generate enough numbers and complete thorough chart reviews (this is where you come in!).
Responsibilities: Chart review to compile pre- and post-surgical changes in corneal dimensions and refraction.
Faculty Advisor: V. Vinod Mootha, M.D.
Sagar Y. Patel, M.D. (PGY3)
Project: This project entails creating a database of patients from Parkland and JPS with recurrent pterygia complicated by symblepharon formation and identifying potential risk factors (race, age, medications, surgical technique). It would be the first study attempting to identify risk factors of this complication, therefore making it very publishable.
Responsibilities: The medical student responsibility would be to assist in reviewing charts and compiling the database.
Faculty Advisor: Ronald Mancini, M.D.
Shaam Mahasneh, M.D. (PGY2)
Project: ORA (Optiwave Refractive Analysis) is a new real-time method of intraoperative refractive biometry (IRB) for intraocular lens (IOL) power calculation providing power, sphere, and axis recommendations. Its introduction into the operating room has been in hopes of significantly increasing accuracy of lens power and axis selection and decreasing prediction error compared to the conventional pre-operative calculation methods.
This study will investigate the effect of ORA on various end-points post-operatively and evaluate the use and outcomes of ORA for IOL power calculations in eyes undergoing cataract surgery versus those of the conventional pre-operative calculation method without Verion to better delineate the efficiency of this new technology.
Responsibilities: Assist with data extraction from EMR into an Excel sheet for data analysis.
Faculty Advisor: R. Wayne Bowman, M.D.
Robert Beaulieu, M.D. (PGY2)
Project: This project will look at the long-term visual outcomes of anti-vascular endothelial growth factor (anti-VEGF) medications for neovascular macular degeneration. We will collect patient data from the Parkland Hospital clinic and look at visual acuity and structural outcomes (i.e. geographic atrophy) over time of patients who have received multiple anti-VEGF treatments more than two years.
Responsibilities: As a part of the team, the medical student will look at patient charts and collect data such as visual acuity at different visits, the number of treatments received, and the specific medications used, which will be entered into a study database. Depending on interest, the medical student can also participate in statistical analysis, data interpretation, and manuscript writing.
Faculty Advisor: Yu-Guang He, M.D.
Linda Yang, M.D. (PGY2)
Project: This project will review the surgical outcomes of optic nerve sheath fenestration (ONSF) for advanced pseudotumor cerebri at Parkland and UTSW. ONSF is not performed as often at other institutions. This study will amass the largest database of patients with ONSF, and therefore will be publishable.
Responsibilities: The medical student will review patient charts and compile the database.
Faculty Advisor: Ronald Mancini, M.D.