Alapakkam Sampath Laboratory
Phototransduction and Synaptic Transmission
Understanding visual processing in the retina
Alapakkam Sampath, Ph.D.
Professor
- Grace and Walter Lantz Endowed Chair in Ophthalmology
- Departments of Ophthalmology and Neurobiology
- Associate Director of Research
- Jules Stein Eye Institute
The goal of the Sampath laboratory is the elucidation of fundamental mechanisms of visual processing. We have focused on generating a deeper understanding of development and signaling between photoreceptor cells—the rods and cones—and their synaptic partners, the bipolar cells, to determine how information is formed and processed within retinal circuits.
Our research focuses on the following questions:
- How can rod photoresponses in the mammalian retina provide such an enormous range of rod vision - from single-photon responses in few rods to light bright enough to activate thousands or tens of thousands of rhodopsin pigment molecules per second?
- How do the many mechanisms of pigment regeneration influence photoreceptor and circuit-level sensitivity in steady light?
- What are the molecules that determine the specificity of synaptic connections between photoreceptors and bipolar cells during development? How are rod and cone photoresponses integrated in the outer retina to provide a seamless shift from rod vision to cone vision as the light intensity increases?
- What is the role of retinal remodeling in controlling visual sensitivity during photoreceptor degeneration? How is this remodeling affected when vision is restored with gene therapy?
- How is retinal structure and function altered or conserved across the animal kingdom? What are the implications of these similarities and differences for the evolution of the vertebrate retina?
These questions remain of great interest because of the large proportion of visual deficits arising from abnormal signaling, either within the phototransduction cascade or in synaptic transmission from photoreceptor terminals to bipolar cells. To answer these questions, we employ classical (but still state-of-the-art) physiological techniques to measure light-evoked responses of photoreceptors, bipolar cells, and ganglion cells, which let us determine how the functional properties of responses are constructed by the retinal circuitry.
Lab Members
Project Scientists
Graduate Students
Kyle Kim
PhD Candidate
My broad interests largely focus on the mechanisms of neurodegenerative diseases. My current dissertation work focuses on how bipolar cells respond to loss of photoreceptor input in retinal degeneration (i.e. retinitis pigmentosa).
Christopher Meredith
PhD Student
Through the use of microspectrophotometry and ex-vivo electroretinograms, Chris investigates the light-driven visual pigment regeneration that allows cones to remain sensitive to stimuli. While his primary focus is on cones, he has also done work studying the effects of pigment lifetime in rod dark adaptation.
Undergraduate Students
Noah St Clair(he/him)
Undergraduate
Noah investigates the metabolic mechanisms underlying retinal photoreceptor function. Using ex vivo electroretinography (ERG) in isolated mouse retinas, he examines how glucose availability, alternative metabolic substrates, and oxygen tension influence photoreceptor responses.
Sanjana Iyer(she/her)
Undergraduate
Sanjana investigates the origin of vertebrate vision by characterizing the retina of hagfish, using ex-vivo electroretinography (ERG) and semithin section staining to explore its electrophysiology and cellular organization.
Recent Publications
Prolonged rod photoresponse and enhanced cone sensitivity in the transgenic mouse retina lacking arrestin and guanylate cyclase activating proteins
Shinya Sato, Rikard Frederiksen, Alapakkam P. Sampath, Vladimir J. Kefalov
The Journal of Physiology (2026)
View PublicationE122Q rhodopsin: pigment microspectrophotometry, photoreceptor light responses, and bleaching adaptation
Christopher J. Meredith, Annabelle N. Tran, Alapakkam P. Sampath, Gordon L. Fain, Rikard Frederiksen
Journal of Comparative Physiology A (2026)
View PublicationConservation of cis-regulatory codes over half a billion years of evolution.
Yohey Ogawa, Yu Liu, Connie A. Myers, Ala Morshedian, Gordon L. Fain, Alapakkam P. Sampath, Joseph C. Corbo
Science advances (2025)
View PublicationPhotoreceptor degeneration induces homeostatic rewiring of rod bipolar cells
Paul J. Bonezzi, Rikard Frederiksen, Annabelle N. Tran, Kyle Kim, Gordon L. Fain, Alapakkam P. Sampath
Current Biology (2025)
View PublicationThe Role of the Ca2+-activated Cl− Conductance in the Membrane Potential and Light Response of Mouse Rods
Rikard Frederiksen, Paul J. Bonezzi, Gordon L. Fain, Alapakkam P. Sampath
The Journal of Neuroscience (2025)
View PublicationTemporal Transformation of the Rod Single-Photon Response in the Retinal Circuitry.
Haruhisa Okawa, Alapakkam P. Sampath
Investigative ophthalmology & visual science (2025)
View PublicationEvolution of rod bipolar cells and rod vision
Rikard Frederiksen, Yi‐Rong Peng, Alapakkam P. Sampath, Gordon L. Fain
The Journal of Physiology (2025)
View PublicationMolecular characterization of the sea lamprey retina illuminates the evolutionary origin of retinal cell types
Junqiang Wang, Lin Zhang, Martina Cavallini, Ali Pahlevan, Junwei Sun, Ala Morshedian, …, Alapakkam P. Sampath, et al.
Nature Communications (2024)
View PublicationA new mouse model for PRPH2 pattern dystrophy exhibits functional compensation prior and subsequent to retinal degeneration.
Breyanna L Cavanaugh, Michelle L Milstein, R Casey Boucher, Sharon X Tan, Mario W Hanna, Adam Seidel, …, Alapakkam P Sampath, et al.
Human molecular genetics (2024)
View PublicationRDH12 allows cone photoreceptors to regenerate opsin visual pigments from a chromophore precursor to escape competition with rods.
Joanna J. Kaylor, Rikard Frederiksen, Christina K. Bedrosian, Melody Huang, David Stennis-Weatherspoon, Theodore Huynh, …, Alapakkam P. Sampath, et al.
Current biology : CB (2024)
View Publication