Impactful mentoring: A catalyst for my journey into research

Despite being a Visual Neuroscientist today, my research journey began in Paleontology as an undergraduate at the Lebanese University, Lebanon, in 2006. Studying fossils from multiple excavation trips, our team described the paleo-environment of a mountain in North Lebanon during the Miocene epoch (circa 20 million BC). This experience was my introduction to hypothesis-driven research and the invaluable role of mentorship. My mentors, Raymond Geze and Dany Azar, were not only humble and inspiring but also dedicated, patient, and detail-oriented, teaching me the essentials of rigorous scientific inquiry and hard work. Our six-month effort led to my Master’s thesis and new discoveries in the field of paleontology in the region. This pivotal experience cemented my passion for research.

With limited PhD opportunities in politically unstable Lebanon, I relocated to Lyon, France, in 2007, to advance my academic career. There, as a Master’s student and subsequently a PhD candidate in Neuroscience under the mentorship of the exceptionally didactic and thorough Claude Gronfier and Howard Cooper at the University of Lyon 1, I studied the newfound non-visual responses to light.

A fossilised Clypeaster (cake urchin). A principal echinoderm of the Upper Miocene.

Studying non-visual responses to light: Uncovering the essence and challenges of research

Light detected through the eyes has a profound influence on human health, cognition, and well-being. For instance, light is fundamental for the visual perception of the world in all its colourful and fine-grained details. Visual perception is mediated by light-sensitive cells (i.e., cones and rods) embedded in the neuronal layer in the back of our eyes, the retina. A little over 22 years ago, an additional type of light-sensing cells was discovered in the mammalian retina: the intrinsically photosensitive retinal ganglion cells (ipRGCs). It is noteworthy, however, that to this day, many undergraduate and medical students are still taught that rods and cones are the only light-sensitive cells in the human retina. ipRGCs are light-sensitive thanks to a special photopigment that they express called melanopsin^1–3, which is predominantly sensitive to blue light (~480nm).⁴ These cells integrate signals from rods, cones, and melanopsin and project to a variety of non-image forming centres in the brain to primarily drive non-visual responses to light such as the entrainment of the circadian system,⁵ the pupillary light reflex,^6–8 melatonin suppression,⁹ eye movements,¹⁰ alertness, cognition, and mood.^11–13

My PhD project assisted in the unveiling of the neurophysiology of non-visual, ipRGC-driven, photoreception in humans. The journey, however, was far from smooth. While my research confirmed earlier findings that peak non-visual sensitivity occurs in the blue-wavelength region of the visible light spectrum (~484 nm), our hypothesis that increased lens yellowing with age, leading to cataracts, would reduce melatonin suppression by blue light was not supported. In fact, non-visual responses to light were not diminished at all by the ageing, blue-filtering crystalline lens.^14,15 Although I initially felt disheartened by what seemed like “negative results,” this experience taught me valuable lessons. I learnt that thoroughness in protocol design, data collection, and analysis is crucial, not just to convince peer reviewers but for my own confidence in publishing trustworthy findings. Despite the contradictory nature of our results, they were eventually published in a renowned peer-reviewed journal after four rigorous rounds of rebuttals. A few weeks later, subsequent research confirmed our findings, suggesting the presence of ocular compensatory mechanisms in response to changes in ocular light transmittance. This challenging yet rewarding journey prepared me for endeavours to come and taught me the importance of being thorough, accepting and addressing criticism openly, and believing that persistence and hard work will lead to success.

First steps into translational research: Light therapy for chronobiological disorders

From a translational perspective, the fundamental biological discovery of ipRGCs has led to a growing interest in re-understanding how to craft light exposure and lighting environments to holistically support not only vision but also overall human physiology. During my PhD in France, and my postdoctoral fellowship in Jamie Zeitzer’s laboratory at Stanford University, US, I led interventional studies in-lab¹⁶ and at the French-Italian Antarctic Base (Concordia)¹⁷ to show that light can be spectro-temporally tuned to increase its impact for overcoming temporary and chronic circadian disorders (e.g., jetlag, delayed sleep phase disorder) but also decrements in well-being and alertness in environments where access to sunlight is sparse such as polar and space stations, submarines, or even elderly homes and some workspaces.

Repurpose your knowledge: Detecting ocular diseases using non-visual responses to light

Handheld chromatic pupillometer developed at SERI.

Like vision, ocular diseases can affect non-visual functions, ranging from acute effects such as a reduced pupillary response to light to chronic effects on alertness and sleep. In 2015, I joined the Visual Neurosciences Group led by Dan Milea at the Singapore Eye Research Institute (SERI). There I focused on improving early detection of ocular diseases, using non-traditional methods tapping on non-visual photoreception and pupillary light responses. Glaucoma is the predominant cause of irreversible blindness worldwide, yet, 70% of glaucoma patients in Singapore are incognisant of their condition. Today, there are no cost-effective screening approaches for glaucoma. Thanks to an unfailing collaboration with glaucoma specialists and neuro-ophthalmologists, we developed and patented¹⁸ a handheld chromatic pupillometer that allowed for a rapid (one-minute test) and accurate detection of glaucoma.¹⁹

This device requiring no expertise and easily implementable into screening programmes will soon be utilised in multiple collaborative studies between SERI, National University Hospital (NUH), and National University of Singapore (NUS) Ophthalmology for the early quantification and detection of retinal dysfunction in patients with ocular and neurological diseases.

Repurpose your knowledge to focus on community needs: Light for a scalable myopia prevention in Singapore

One of the main reasons I chose to come to Singapore was my keen interest in myopia and the promising role of light in its prevention. I recognised that this research area would allow me to effectively combine my expertise in chronobiology, photobiology, and vision science to maximise impact. In 2023, I founded the Eye N’ Brain Research Group at NUS and became the head of the Visual Neurosciences Research Group at SERI. My teams’ current research focuses on understanding and mitigating non-visual consequences of visual impairment and understanding and developing scalable light therapy strategies for myopia.

The Eye N’ Brain Research Group at NUS and the Visual Neuroscience Group at SERI.

Studying the impact of the light spectrum on ocular growth and cognition.

In fact, in 2023, with the support of the National Research Foundation, Project LightSPAN was launched. This ambitious collaboration, involving NUS, TUMCREATE, SERI, Stanford, and other institutions, draws on our recent findings in animal models, to evaluate the efficacy, safety, and feasibility of two scalable interventions (improved classroom lighting and a digital behaviour-tuning intervention) on improving light exposure in children aged seven to 10 years for myopia prevention and control. This school-based trial was launched in October 2024. We are hopeful that in the upcoming two years, our open collaboration with local and international stakeholders will enable us to ultimately ensure scalability and widespread adoption of our findings, with the hope to make a lasting impact on alleviating myopia prevalence in Singapore and Asia.

Final thoughts

Reflecting on my journey from paleontology to visual neuroscience, the pivotal role of mentorship and the dedication to rigorous science have been the cornerstones of my career. Starting with hypothesis-driven research in Lebanon, I transitioned to discovering crucial insights on the impact of light on human physiology. These foundational experiences paved the way for my translational research endeavours at Stanford and France, where we explored light therapy’s potential to address chronobiological disorders. A big part of my move to Singapore was driven by a commitment to halting myopia. It is a commitment fuelled by numerous nurturing collaborations at NUS and SERI and exemplified by project LightSPAN, bringing scalable and safe myopia interventions from bench to classrooms.

Click here to find out more about the work of Eye N’ Brain Research Group.

Click here to find out more about Project LightSPAN.