Research

The Chen Lab explores how pupil reactivity can serve as a noninvasive biomarker for brain aging and neurodegenerative disease. By studying the neural pathways that regulate the pupil—such as the Edinger-Westphal nucleus and Locus Coeruleus—we investigate links between pupil responses, cognitive decline, and early Alzheimer’s pathology. Our goal is to better understand how subtle changes in the eye reflect broader changes in brain health.

Areas of Research

Edinger-Westphal Nucleus and Pupil Constriction

Pupil response to light is shaped by brain activity in the Edinger-Westphal nucleus. This response may reflect early Alzheimer’s changes tied to acetylcholine and cognitive function.

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The pupil constriction to light stimulation is modulated by the brain parasympathetic Edinger-Westphal nucleus. Acetylcholine, the neurotransmitter underlying the pathophysiologic process of Alzheimer’s disease, may also modulate the correlation between pupil constriction to light and neuropsychologic cognitive measures.

ipRGCs and Cognitive Function

Specialized retinal cells (ipRGCs) link light perception to brain centers that regulate circadian rhythms and cognition. Their role in pupil response may reveal early signs of cognitive decline.

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The intrinsically photosensitive retinal ganglion cells (ipRGCs), a group of novel, melanopsin-containing photoreceptors in the inner retina that connect the eyes to the brain hypothalamus suprachiasmatic nuclei, provide the primary anatomic substrate for circadian rhythm and various other nonimage-forming functions, including cognition. The ipRGC-associated pupil reactivity is correlated with neuropsychologic cognitive measures. The mechanism behind this correlation has yet to be elucidated.

Locus Coeruleus and Alzheimer’s Detection

The Locus Coeruleus is an early site of Alzheimer’s pathology. Changes in pupil reactivity may offer a noninvasive window into its function and degeneration.

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Is the pupil a reliable readout of the Locus Coeruleus (LC) activity? The brainstem LC nucleus is the brain noradrenergic hub that plays an integral role in regulating arousal, attention, memory, and decision-making. The LC nucleus demonstrates the earliest Alzheimer-like pathologic changes. Can alteration of pupil reactivity be used as a readout of the LC degeneration in Alzheimer’s disease?