About

Gordon Fain is a Distinguished Professor who received his BA in Biology from Stanford University and his PhD in Biophysics from Johns Hopkins University. After completing postdoctoral research at Harvard and the École Normale Supérieure in Paris, he joined UCLA in 1975 and remained there for his entire career. He is a Gugenheim fellow, NIH MERIT scholar, and Fellow of the AAAS. Although he retired from active service in 2017, he continues his research funded by the NIH. His research focuses on the mechanisms of vertebrate photoreceptors, particularly the G-protein receptor rhodopsin and its cascade, which produce electrical responses signaling changes in light intensity. He employs genetic techniques to study the roles of various proteins involved in the visual cascade, using electrical recordings to understand their functions in mouse rods and cones, with a special interest in modulatory enzymes and mechanisms of photoreceptor degeneration in inherited diseases.

Research topics

• Biology
• Biophysics
• Optics
• Computer Science
• Physics
• Neuroscience
• Anatomy
• Biochemistry
• Cell biology
• Endocrinology
• Physiology
• Medicine
• Chemistry

Selected publications

• The Role of the Ca²⁺-activated Cl⁻Conductance in the Membrane Potential and Light Response of Mouse Rods

  Journal of Neuroscience · 2025-04-25

  articleOpen access

  To characterize the function of the Ca 2+ -activated Cl − current I Cl(Ca) in mammalian rod photoreceptors, we made patch-clamp recordings from retinal slices of mice ( Mus musculus ) of both sexes that lack Ano2 (TMEM16B). Depolarizing voltage ramps in solutions blocking K + currents elicited a large outward current inhibited by the Cl − channel blocker niflumic acid; this current was absent in Ano2 −/− rods. The membrane potential of Ano2 −/− rods was 10–15 mV more depolarized in darkness than WT or Cx36 −/− rods, indicating a substantial resting Cl − permeability. Rod outer-segment photocurrents were similar in waveform and amplitude in Ano2 −/− and Cx36 −/− rods, but photovoltages in Ano2 −/− rods were nearly doubled. Measurements of light-response reversal potentials in rods with and without Ano2 suggest that the outer-segment conductance is nearly linear with a reversal potential of −9 mV and that <m:math xmlns:m="http://www.w3.org/1998/Math/MathML" display="inline" overflow="scroll"> <m:mi mathvariant="normal">Δ</m:mi> <m:msub> <m:mi>g</m:mi> <m:mrow> <m:mrow> <m:mi mathvariant="normal">Cl</m:mi> </m:mrow> </m:mrow> </m:msub> </m:math> increases during the light response. Using these results, we estimated E Cl from permeabilized patch recordings of reversal potentials of Cx36 −/− rods to have a mean value of −35 mV near the rod resting potential, but other evidence suggests that E Cl may be more positive by as much as 10–15 mV. Thus activation of I Cl(Ca) during the light response would be depolarizing. At dim intensities, the photocurrents of downstream rod bipolar cells were larger and about twice as sensitive in Ano2 −/− retinas with reduced nonlinearity. These experiments show that Ca 2+ -activated Cl − currents in mammalian rods have more important roles in photoreceptor physiology than previously appreciated.

  PublisherOA PDFDOI

• The physiology of dark adaptation: Progress and future directions

  Progress in Retinal and Eye Research · 2025-09-27

  review1st authorCorresponding
  PublisherDOI

• Evolution of rod bipolar cells and rod vision

  The Journal of Physiology · 2025-01-07 · 6 citations

  reviewOpen accessSenior authorCorresponding

  Bipolar cells are vertebrate retinal interneurons conveying signals from rod and cone photoreceptors to amacrine and ganglion cells. Bipolar cells are found in all vertebrates and have many structural and molecular affinities with photoreceptors; they probably appeared very early during vertebrate evolution in conjunction with rod and cone progenitors. There are two types of bipolar cells, responding to central illumination with depolarization (ON) or hyperpolarization (OFF). In most vertebrate species, rod signals are conveyed to specialized rod bipolar cells, which sum signals from many rods and facilitate detection at the visual threshold. Lamprey, which diverged from all other vertebrates in the late Cambrian, have both rod ON and rod OFF bipolar cells, but mammals have only rod ON cells. Rod signals in mammals are conveyed to output neurons indirectly via AII (or A2) amacrine cells, which synapse onto cone ON and cone OFF bipolar-cells and then to ganglion cells. These findings raise the question of when during retinal evolution rod OFF bipolar cells were lost. Because physiological recordings have been made from rod OFF bipolar cells in both cartilaginous fishes (dogfish) and urodeles (salamanders), rod OFF bipolar cells and their circuits must have been retained in vertebrate progenitors at least until the Devonian. Recent evidence showing that zebrafish retina processes rod signals similar to those in mammals indicates that rod OFF bipolar cells were lost at least twice. The sole utilization of rod ON bipolar cells may have provided a selective advantage from increased signal-to-noise discrimination near the visual threshold. KEY POINTS: Rods and cones have many structural and molecular similarities to bipolar cells, which are retinal interneurons conveying signals from photoreceptors to the retinal output. Bipolar cells can be either ON (centre depolarizing) or OFF (centre hyperpolarizing) and either rod or cone dominant. Lamprey, which diverged from all other vertebrates 500 million years ago, have both ON and OFF bipolar cells, which can each be either rod or cone dominant. We argue that this configuration of separate rod/cone bipolar-cell pathways is representative of early vertebrates. Rod ON and rod OFF bipolars persisted at least until the progenitors of amphibians in the Devonian, but mammals and teleost fishes have only rod ON bipolar cells and convey rod OFF signals via a specialized amacrine cell. We argue that rod OFF bipolar cells were lost in at least two different lineages during vertebrate evolution, probably to increase the signal-to-noise of rod vision.

  PublisherOA PDFDOI

• Conservation of cis-regulatory codes over half a billion years of evolution

  Science Advances · 2025-12-12 · 1 citations

  articleOpen access

  Identifying homologous cell types across species is essential for understanding cell type evolution. The retina is ideal for comparative analysis because its six major cell classes have persisted since the origin of vertebrates more than half a billion years ago. Here, we show that the retina's conserved cellular architecture is mirrored by deep conservation of the cis-regulatory codes that govern gene expression. Through single-cell chromatin accessibility analysis of lamprey, fish, bird, and mammalian retinas, we demonstrate cross-species conservation of cis-regulatory codes in all retinal cell classes despite extensive turnover of cis-regulatory regions. Conservation manifests as clustering of high-affinity transcription factor binding sites in cell class-specific open chromatin regions. Thus, the retina's cellular Bauplan is controlled by cis-regulatory codes, which predate the divergence of extant vertebrates.

  PublisherDOI

• Photoreceptor degeneration induces homeostatic rewiring of rod bipolar cells

  Current Biology · 2025-06-25 · 1 citations

  articleOpen access
  PublisherOA PDFDOI

• Molecular characterization of the sea lamprey retina illuminates the evolutionary origin of retinal cell types

  Nature Communications · 2024-12-30 · 15 citations

  articleOpen access

  The lamprey, a primitive jawless vertebrate whose ancestors diverged from all other vertebrates over 500 million years ago, offers a unique window into the ancient formation of the retina. Using single-cell RNA-sequencing, we characterize retinal cell types in the lamprey and compare them to those in mouse, chicken, and zebrafish. We find six cell classes and 74 distinct cell types, many shared with other vertebrate species. The conservation of cell types indicates their emergence early in vertebrate evolution, highlighting primordial designs of retinal circuits for the rod pathway, ON-OFF discrimination, and direction selectivity. The diversification of amacrine and some ganglion cell types appears, however, to be distinct in the lamprey. We further infer genetic regulators in specifying retinal cell classes and identify ancestral regulatory elements across species, noting decreased conservation in specifying amacrine cells. Altogether, our characterization of the lamprey retina illuminates the evolutionary origin of visual processing in the retina.

  PublisherOA PDFDOI

• Genetic manipulation of rod-cone differences in mouse retina

  PLoS ONE · 2024-05-06

  articleOpen access

  Though rod and cone photoreceptors use similar phototransduction mechanisms, previous model calculations have indicated that the most important differences in their light responses are likely to be differences in amplification of the G-protein cascade, different decay rates of phosphodiesterase (PDE) and pigment phosphorylation, and different rates of turnover of cGMP in darkness. To test this hypothesis, we constructed TrUx;GapOx rods by crossing mice with decreased transduction gain from decreased transducin expression, with mice displaying an increased rate of PDE decay from increased expression of GTPase-activating proteins (GAPs). These two manipulations brought the sensitivity of TrUx;GapOx rods to within a factor of 2 of WT cone sensitivity, after correcting for outer-segment dimensions. These alterations did not, however, change photoreceptor adaptation: rods continued to show increment saturation though at a higher background intensity. These experiments confirm model calculations that rod responses can mimic some (though not all) of the features of cone responses after only a few changes in the properties of transduction proteins.

  PublisherOA PDFDOI

• Retinal Processing Strategies: How Adaptational Mechanisms Shape the Dynamic Range of Vision

  Elsevier eBooks · 2024-05-30

  book-chapterCorresponding
  PublisherDOI

• RDH12 allows cone photoreceptors to regenerate opsin visual pigments from a chromophore precursor to escape competition with rods

  Current Biology · 2024-07-08 · 13 citations

  articleOpen access
  PublisherOA PDFDOI

• Conservation of <i>cis</i> -regulatory codes over half a billion years of evolution

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-11-14 · 3 citations

  preprintOpen access

  ABSTRACT The identification of homologous cell types across species represents a crucial step in understanding cell type evolution. The retina is particularly amenable to comparative analysis because the basic morphology, connectivity, and function of its six major cell classes have remained largely invariant since the earliest stages of vertebrate evolution. Here, we show that the retina’s highly conserved cellular architecture is mirrored by deep conservation of the underlying cis -regulatory codes that control gene expression. We use comparative single-cell chromatin accessibility analysis of lamprey, fish, bird, and mammalian retinas— representing over half a billion years of evolutionary divergence—to demonstrate cross-species conservation of cis -regulatory codes in all six retinal cell classes. This conservation persists despite extensive turnover of cis -regulatory regions between distant species. Conservation manifests as the clustering of multiple distinct high-affinity transcription factor (TF) binding sites toward the center of cell-class-specific open chromatin regions with little cross-species preservation of higher-order syntax. Hierarchical clustering of machine-learning models of retinal cis -regulatory codes from diverse species recovers six clusters corresponding to the six retinal cell classes. Thus, the retina’s cellular Bauplan is controlled by cis -regulatory codes which predate the divergence of extant vertebrates and persist despite nearly complete enhancer turnover.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01EY007568

  NIH · $1.7M · 1998

• NIH Grant R37EY001844

  NIH · $2.6M · 2000

• Physiology of Photoreceptors

  NIH · $10.7M · 1984–2026

• Vision Science Training Program

  NIH · $8.1M · 1975–2027

Frequent coauthors

• Alapakkam P. Sampath

  University of California, Los Angeles

  78 shared

• Michael L. Woodruff

  East Tennessee State University

  67 shared

• M. Carter Cornwall

  Boston University

  57 shared

• Ala Morshedian

  University of California, Los Angeles

  40 shared

• Hugh R. Matthews

  Physiological Society

  35 shared

• H.R. Matthews

  Physiological Society

  35 shared

• Yiannis Koutalos

  Medical University of South Carolina

  25 shared

• Marianne Cilluffo

  University of California, Los Angeles

  25 shared

Labs

• Integrative Biology and PhysiologyPI

  First Years Second Years Continuing Students

Education

• Ph.D., Biology

  University of California, Los Angeles

  1994

• B.S., Biology

  University of California, Los Angeles

  1989

Awards & honors

• Gugenheim fellow
• NIH MERIT scholar
• Fellow of AAAS