RESEARCH

Research Interests:

The research interests in Dr. Linn's lab are involved with visual information processing and disease states of the vertebrate retina.  One major focus in her lab deals with neuroprotection against glutamate-induced excitotoxicity using an in vitro and in vivo model of glaucoma.  In the in vitro studies, adult pig and rat retinal ganglion cells are isolated from other retinal neurons and cultured under excitotoxic-inducing conditions.  Studies in the lab have identified a number of neuroprotective agents that prevent excitotoxicity and cell loss of  the ganglion cells.  Current research is identifying and analyzing the mechanisms involved in neuroprotection using a combination of pharmacological, electrophysiological and ELISA methodology.  In the in vivo studies, various neuroprotective agents are assessed to determine their effect on loss of retinal ganglion cells that are associated with glaucoma-like conditions.

Small pig retinal ganglion cells isolated from retinal tissue contain α4β2 nAChR subunits.  Antibodies specific against α4 nAChR subunits were secondarily labeled with Texas Red (A).  Antibodies specific against β2 nAChR subunits were secondary labeled with Alexa Fluor 488 (B).  (C) Demonstrates that both nAChR subunits are colocalized on small pig RGCs  (Thompson et al., 2006). 

Mechanism of neuroprotection against glutamate-induced excitotoxicity in isolated adult pig retinal ganglion cells.  Activation of nAChRs trigger the PI3 kinase - Akt - Bcl2 neuroprotective pathway while inhibiting  p38 MAPK that is associated with apoptosis in these cells (Asomugha et al., 2010).

 Control Untreated Retina                    Experimental Retina

The cell bodies of rat RGCs from a control untreated retina were stained and are shown in the left figure.   The cell bodies of RGCs from the same region of the retina in the glaucoma-induced eye are shown in the right figure.  There is a 25% reduction in cell bodies after inducing glaucoma.                    

Technical Expertise in:

1) Electrophysiology:

• a) voltage-clamp whole-cell techniques
• b) patch-clamp techniques
• c) single channel recording from on-cell and excised outside-out patches

2) Fluorescent imaging techniques

3) Neuropharmacology

4) Cell culture techniques

5) Immunocytochemistry

6) Calcium Imaging

Potential Lab Projects:

 *     Development of an in vivo glaucoma model to analyze the effects of neuroprotective agents on retinal ganglion cell

        survival.

*     Analysis of the mechanism involved in neuroprotection against glutamate-induced excitotoxicity

*     Effect of ACh as a neuroprotective agent in the retina