Research Seminar

This semester, students from the Research Committee will share their research areas and findings. This will allow us to understand each other’s research focus and methodology in different areas of biomedical science, enhance academic exchange, and hone our research presentation skills. Each issue will also include a brief description of the relevant R&D companies for reference.

– Speaker: HJP –

InT@UCLA Research Committee Director,
Work study @ Dr. Jie Zheng Lab at Stein Eye Institute, David Geffen School of Medicine at UCLA.
“Pre-PhD with dreams of building my own lab or biomedical company.

Love fitness, cooking, muscle cars, and classical music.
Responsibility, integrity, and not giving up are my mottos.”

1 Why do we care about glaucoma?

Glaucoma is the number one cause of vision impairment as well as blindness. Although glaucoma is often understood as a disease of old age, I am surrounded by a number of students who have high intraocular pressure as well as unhealthy eye habits (e.g., staying up all night using their smartphones), which are potential contributing factors to glaucoma.

The eyes are the windows to the soul, and I hope that I can make a small contribution to stopping more blindness from occurring through my research.

Where does glaucoma come from?

Elevated intraocular pressure (IOP) is the primary cause of ocular hypertension. If the intraocular pressure is left unchecked for a long time, the extremely high pressure inside the eye can damage the optic nerve and lead to visual impairment and, in severe cases, irreversible blindness, which is how glaucoma develops.

There are many different types of glaucoma. Here are 2 of the most common ones:

Primary open-angle glaucoma is caused by rising intraocular pressure.

• It may be associated with a family history of glaucoma, high intraocular pressure that has been left untreated, diabetes mellitus, high myopia, and a thin central corneal thickness.

Secondary glaucoma develops as a result of specific pathologic factors.

• Such as long-term steroid use, blockage of the trabecular meshwork by inflammatory cells/damaged tissue cells caused by some primary eye diseases, etc.

What are the symptoms of glaucoma?

Usually, there are no symptoms in the early stage, and the condition will progress to a certain level with blurred vision, eye swelling, headache, and other manifestations. In the advanced stage, there will be obvious visual impairment or blindness.

What are the current treatment options?

Medication (focusing primarily on lowering intraocular pressure):

• Prostaglandin derivatives (increase atrial fluid drainage)
• Adrenergic receptor blockers (reduce atrial water production)
• Cholinomimetic drugs (increase atrial fluid excretion)
• Carbonic anhydrase inhibitors (reduce atrial water production)

Surgical treatment:

• Trabeculectomy (medicine)
• Glaucoma drainage device implant

2 What are the latest trends in glaucoma research?

One focus of glaucoma research is the trabecular meshwork tissue.

As shown by the arrows in the image below, the trabecular meshwork is located at the junction of the cornea and iris and is responsible for regulating and controlling the circulation of aqueous humor. If the trabecular meshwork is damaged or abnormal, the circulation of aqueous humor is no longer regulated, leading to an increase in intraocular pressure, which may ultimately lead to the development of glaucoma.

Trabecular meshwork cells undergo many changes in glaucomatous pathology, including changes in morphology, significant increases or decreases in the expression of specific genes, aggregation of the extracellular matrix, and increases in the cytoskeleton.

Dexamethasone is the most common and widely used glucocorticoid. Numerous studies and clinical data have demonstrated that prolonged treatment with glucocorticoid eye drops or systemic therapy can induce an increase in intraocular pressure (IOP), which can lead to steroid-induced glaucoma.

Since there are many similarities between primary open-angle glaucoma and steroid-induced glaucoma at the molecular biology level, researchers generally use dexamethasone to induce trabecular meshwork cells to form the pathologic state corresponding to glaucoma. This is the most common in vitro disease model used in glaucoma research.

3 Our research?

Our laboratory is very interested in the altered expression of the WNT pathway (shown below) in steroid-induced glaucoma models.

Current studies have shown that steroid treatment leads to a significant increase in the expression of the WNT pathway in trabecular meshwork cells, so we often test some of our small molecule drugs designed based on the WNT pathway, the results of which can be found at the following link: www.uclahealth.org/departments/eye/research/research-laboratories/therapeutic-development-ophthalmology/publications

4 What are the industries associated with glaucoma treatment?

Diagnosis:

Glaucoma is the second most common irreversible blinding eye disease in China. However, there are only 30,000 ophthalmologists in China, and even in areas such as Beijing and Guangzhou, where China has pooled a large number of ophthalmic medical resources, the diagnostic coverage of primary glaucoma is only 18.0% to 20.3%.

In recent years, artificial intelligence-assisted screening systems based on color fundus pictures have provided cost savings in glaucoma screening, allowing screening to hopefully reach a wider population (Chen et al.)

Fundus image dataset training (www.kaggle.com/c/diabetic-retinopathy-detection/)

Medication:

Sandoz under Novartis (timolol)

Allergan (lumigan bemoprost eye drops)

Santen (Tepros Tafluprost Eye Drops)

Alcon (suvastatin travoprost eye drops, betaxolol hydrochloride eye drops)

Other pharmaceutical companies are also active in research and development, such as Pfizer, Merck, Ocular Therapeutix, Icon Bioscience, Amorphex Therapeutics, Ellex, Quantel, Lumenis, Lightmed, etc (Zhihu).

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References

Chen, Binbin, et al. “Eye Diseases Burden in China in the Past 30 Years.” Zhejiang Da Xue Xue Bao. Yi Xue Ban = Journal of Zhejiang University. Medical Sciences, Zhejiang University Press, 25 Aug. 2021, doi: 10.3724/zdxbyxb-2021-0246. 

Fini, M. Elizabeth, et al. “Steroid-Induced Ocular Hypertension/Glaucoma: Focus on Pharmacogenomics and Implications for Precision Medicine.” Progress in Retinal and Eye Research, Pergamon, 22 Sept. 2016,

https://doi.org/10.1016/j.preteyeres.2016.09.003

Lal, Maria, et al. “Novel Approaches for Ocular Targeted Drug Delivery Systems.” IJPPR, Human Journals, Feb. 2022, https://ijppr.humanjournals.com/novel-approaches-for-ocular-targeted-drug-delivery-systems/. 

Laureano, Joseph San. “Closed Angle Gglaucoma Explanation.” Melbourne Eye Centre, 19 Jan. 2020, https://melbourneeyecentre.com.au/glaucoma/closed-angle-glaucoma/. 

Patel, Sonal, et al. “Wnt signaling and its significance within the tumor microenvironment: novel therapeutic insights.” Frontiers in immunology 10 (2019): 2872, https://doi.org/10.3389/fimmu.2019.02872

Quigley, Harry A. “Glaucoma.” The Lancet, Elsevier, 30 Mar. 2011, https://doi.org/10.1016/S0140-6736(10)61423-7

Stamer, W. Daniel, and Abbot F. Clark. “The Many Faces of the Trabecular Meshwork Cell.” Experimental Eye Research, Academic Press, 19 July 2016,

https://doi.org/10.1016/j.exer.2016.07.009

Zhang, Chi et al. “Oxidative stress upregulates Wnt signaling in human retinal microvascular endothelial cells through activation of disheveled.” Journal of cellular biochemistry vol. 120,8 (2019): 14044-14054. doi:10.1002/jcb.28679

“Education.” Bangladesh Glaucoma Society, https://bgsglaucoma.com/education/. 

“青光眼–国际防盲机构.” 国际防盲机构, IAPB Vision Atlas, 13 Apr. 2021, https://www.iapb.org/zh/learn/vision-atlas/causes-of-vision-loss/glaucoma/

许 斯达. “如何分析眼科市场和行业：基本信息和框架.” 知乎专栏, https://zhuanlan.zhihu.com/p/421305872

“2015-2025年青光眼治疗药物行业市场调研报告.” 知乎专栏, 湖南贝哲斯信息咨询有限公司, https://zhuanlan.zhihu.com/p/345865196

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In the next session, we will welcome Yuhan Sun to present a brief overview of neurodegenerative diseases!