Puthussery Lab
Research Interests
The overall goal of our work is to understand how visual information is encoded and transmitted through the retinal circuitry to generate signals that can be interpreted by the higher visual centers in the brain. We are also interested in how retinal connectivity and signaling is altered during retinal neurodegenerative diseases. We use a variety of techniques to address our research questions including: immunohistochemistry, confocal and super-resolution microscopy, two-photon calcium imaging, patch-clamp electrophysiology and protein biochemistry.
Current Projects
We use calcium imaging to study the responses of retinal neurons to different patterns of visual stimulation. This video shows the diverse responses of the output neurons of the retina to a light stimulus.
1. Functional and molecular classification of the output neurons of the retina
A detailed understanding of the normal structure and function of the retina is necessary to appreciate changes that occur during disease, development and aging. To this end, a major goal for the field has been to obtain a unified functional, molecular and morphological classification of the neural cell types in the retina. The human eye contains ~20 different types of ganglion cells, the output neurons that transmit visual information from the retina to the brain. Each of these ganglion cell types is thought to be optimized to extract different features from the visual environment, such as form, motion and color. Although some human ganglion cells have been studied in detail, the functions of many cell types remain poorly understood. We have developed a multimodal approach to study the function and morphology of molecularly-identified ganglion cell types in the ex vivo retina. Our goal is to develop a more complete understanding of what the human eye tells the brain. More details about this project can be found here.
2. Silencing electrical noise in photoreceptor degeneration
Photoreceptor degeneration is a hallmark of a variety of blinding retinal diseases, including age related macula degeneration and retinitis pigmentosa. Studies in animal models show that after photoreceptors die, the ganglion cells exhibit spontaneous electrical activity. This aberrant activity corrupts residual vision and could impair the success of vision restoration. We are investigating the retinal circuit mechanisms that underlie this aberrant activity using a mouse model of inherited retinal degeneration. We are also testing a novel pharmacological approach to suppress aberrant activity. Our hope is to develop therapies to improve visual function in patients with blinding photoreceptor degenerations.
3. Vision restoration in a model of macular degeneration
A variety of methods are being developed to restore visual function after photoreceptor degeneration. We are collaborating with Juliette McGregor (U Rochester) and David Gamm (U Wisc-Madison) to determine how photoreceptor degeneration impacts the structure of neurons of the inner retina in a model of foveal vision loss. We will use this model to determine whether stem-cell derived photoreceptor precursors can mature and integrate with the host retina to restore visual function. This project is funded by an Audacious Goals Initiative Grant from the National Eye Institute. More information about this project can be found here.