The Van Gelder Lab, funded continuously since 1999 by the National Institutes of Health, develops photochemical methods to treat blindness and discover microorganisms associated with various eye diseases, such as ocular infectious diseases, including
microbial keratitis,
conjunctivitis, and
endophthalmitis, which are a significant cause of blinding diseases. Using techniques such as
deep sequencing and other molecular methods, the Van Gelder lab analyzes the host microbiome and analyzes pathologic strains of viruses and bacteria causing inflammatory eye disease. The Van Gelder lab is investigating synthetic small molecule photoswitches as a therapeutic for degenerative blinding diseases (such as
age-related macular degeneration, which is caused by death of rods and cones). The Van Gelder lab is also working to understand mammalian circadian rhythms and studies mouse models to understand clock synchronization using light, cell-level research of light perception, and issues related to
seasonal affective disorder. Eventually, Van Gelder and his coauthors were granted 5 patents for this amplification technique, the most recent in 2006. This technique used a synthetic oligonucleotide primer containing a
T7 RNA polymerase promoter sequence. This was able to generate large quantities (up to 80-fold) of amplified antisense RNA (aRNA) from significantly smaller samples of cDNA.
Intrinsically photosensitive retinal ganglion cells In a 2005
Neuron paper, Van Gelder found that
intrinsically photosensitive ganglion cells (ipRGCs), which are responsible for mediating non-visual processes such as
entrainment, are the first light-sensitive cells in the retina. Using a micro-electrode array in the ipRGCs of
murine mice, Van Gelder found that there are three distinct cell populations in the postnatal day 8 (P8) retina, varying in their speed of onset, offset, and sensitivity. Further investigation found that even the postnatal day 0 retina displayed some intrinsic light response, with increased photosensitivity around day 6. These findings suggest that ipRGCs are the first photosensitive cells in the development of the retina.
Neuropsin-mediated photoentrainment In a 2015
PNAS paper, Van Gelder and colleagues (with first author former postdoctoral fellow Ethan Buhr) found that
Opsin-5 is sufficient for the entrainment of the molecular circadian clock in the mammalian retina. Entrainment to light in the mammalian retina is independent of the suprachiasmatic nucleus (
SCN) and does not require rods, cones, or
melanopsin. While the short-wavelength sensitive cone pigments
OPN1SW and
OPN3 are not required for entrainment, Van Gelder's group found that retinas that lack OPN5, which are expressed in select retinal ganglion cells, are unable to entrain even though these cells still maintain normal visual functions. Additionally, Van Gelder's lab found that OPN5 was sufficient in entraining the circadian rhythms of mice cornea
ex-vivo, ascertaining the function of OPN5, which until then was classified as an orphan opsin.
Detection and treatment of uveitis Van Gelder has worked extensively on the use of
optical coherence tomography (OCT), a non-invasive imaging technique that uses low-coherence light to capture micrometer resolution images. Van Gelder's work in this field has included the use of spectral-domain optical coherence tomography (SD-OCT), which involves the use of a line-scan camera, instead of a spectrometer as is conventionally used in OCT. This allows for faster and higher resolution imaging Van Gelder has used SD-OCT to image the inflammation associated with uveitis in rat models [https://iovs.arvojournals.org/article.aspx?articleid=2533367, as well as other macular degeneration. == Memberships ==