Research Projects
The Kaja laboratory is interested in identifying the pathophysiological mechanisms underlying human ophthalmic, neurological and neurodegenerative disorders. The primary focus of the laboratory is on calcium signaling pathways and inflammatory processes, in particular their involvement in synaptic and physiological dysfunction.
Glaucoma
Glaucoma is the second leading cause of blindness worldwide and causes a substantial burden on the affected individual, caregivers, and society alike. It is estimated that approx. 6 mi Americans are affected by glaucoma.
Primary open-angle glaucoma (POAG) is the most common form of glaucoma and defined as any glaucoma in which the angle of the anterior chamber remains open, but the exit of aqueous through the trabecular meshwork is diminished. This leads to an abnormal balance of secretion and drainage of aqueous through the trabecular meshwork and uveoscleral outflow pathways, ultimately resulting in elevated intraocular pressure (IOP). Currently available therapies can lower IOP by selectively targeting uveaoscleral outflow pathways to prevent further ON damage, however, visual field loss and death of both RGCs and ONHAs continue, highlighting the need for novel treatment strategies.
In the Kaja laboratory, we are interested in developing novel anti-glaucoma therapies that target early disease processes in order to prevent the progressive cascade of glaucomatous changes from occurring.
To this end, we are using a number of in vitro models, including primary culture of retinal ganglion cells, optic nerve head astrocytes as well as genetic and surgical models to induce glaucoma experimentally.
Primary open-angle glaucoma (POAG) is the most common form of glaucoma and defined as any glaucoma in which the angle of the anterior chamber remains open, but the exit of aqueous through the trabecular meshwork is diminished. This leads to an abnormal balance of secretion and drainage of aqueous through the trabecular meshwork and uveoscleral outflow pathways, ultimately resulting in elevated intraocular pressure (IOP). Currently available therapies can lower IOP by selectively targeting uveaoscleral outflow pathways to prevent further ON damage, however, visual field loss and death of both RGCs and ONHAs continue, highlighting the need for novel treatment strategies.
In the Kaja laboratory, we are interested in developing novel anti-glaucoma therapies that target early disease processes in order to prevent the progressive cascade of glaucomatous changes from occurring.
To this end, we are using a number of in vitro models, including primary culture of retinal ganglion cells, optic nerve head astrocytes as well as genetic and surgical models to induce glaucoma experimentally.
Primary culture of adult rat optic nerve head astrocytes. Left: DIC image. Right: Optic nerve head astrocytes labelled with AlexaFluor 488 phalloidin and co-stained with DAPI.
Selected publications:
• Kaja S, Payne AJ, Naumchuk Y, Levy D, Zaidi DH, Altman AM, Nawazish S, Ghuman JK, Gerdes BC, Moore MA, Koulen P. Plate reader-based cell viability assays for glioprotection using primary rat optic nerve head astrocytes. Experimental Eye Research 2015; in press.
• Kaja S, Payne AJ, Patel KR, Naumchuk N, Koulen P. Differential subcellular Ca2+ signaling in a highly specialized subpopulation of astrocytes. Experimental Neurology 2015, 265: 59-68
• Burroughs SL, Kaja S, Koulen P. Quantification of deficits in spatial visual function of mouse models for glaucoma. Invest Ophthalmol Vis Sci. 2011;52(6):3654-9. PMCID: 3109046.
• Kaja S, Payne AJ, Naumchuk Y, Levy D, Zaidi DH, Altman AM, Nawazish S, Ghuman JK, Gerdes BC, Moore MA, Koulen P. Plate reader-based cell viability assays for glioprotection using primary rat optic nerve head astrocytes. Experimental Eye Research 2015; in press.
• Kaja S, Payne AJ, Patel KR, Naumchuk N, Koulen P. Differential subcellular Ca2+ signaling in a highly specialized subpopulation of astrocytes. Experimental Neurology 2015, 265: 59-68
• Burroughs SL, Kaja S, Koulen P. Quantification of deficits in spatial visual function of mouse models for glaucoma. Invest Ophthalmol Vis Sci. 2011;52(6):3654-9. PMCID: 3109046.
Dry Eye Disease
Dry eye disease, also known as keratoconjunctivitis sicca, is
an eye disease caused by eye dryness, resulting from either decreased tear
production or increased tear film evaporation. Dry eye disease is the most
common eye disease affecting 5-6% of the population. One of the most important
risk factors for dry eye disease is age, and prevalence has been reported as
high as 34% in the elderly.
Symptoms of dry eye disease include stinging, burning or scratchy sensations in the eyes, increased eye irritation from smoke or wind, eye fatigue, sensitivity to light, eye redness, foreign body sensations, difficulty wearing contact lenses and periods of excessive tearing. Often patients report blurred vision, worsening at the end of the day or after focusing for a prolonged period.
The tear gland (or lacrimal gland) produces the aqueous component of tears, and lacrimal gland pathology is a hallmark of dry eye disease. Research in the Kaja lab focuses on novel therapeutic strategies that improve lacrimal gland health and restore normal lacrimal gland pathology in order to improve dry eye symptoms. Our approach focuses on antioxidant protection of the lacrimal gland, based on the rationale that elevated oxidative stress levels resulting from corneal inflammation contribute critically to lacrimal gland dysfunction. We employ a number of experimental paradigms, incl. in vitro and in vivo technologies to study dry-disease. A recent focus of the laboratory has been to improve and standardize the induction of dry-eye disease in in vivo models using a combination of environmentally-induced and scopolamine-induced symptoms.
Symptoms of dry eye disease include stinging, burning or scratchy sensations in the eyes, increased eye irritation from smoke or wind, eye fatigue, sensitivity to light, eye redness, foreign body sensations, difficulty wearing contact lenses and periods of excessive tearing. Often patients report blurred vision, worsening at the end of the day or after focusing for a prolonged period.
The tear gland (or lacrimal gland) produces the aqueous component of tears, and lacrimal gland pathology is a hallmark of dry eye disease. Research in the Kaja lab focuses on novel therapeutic strategies that improve lacrimal gland health and restore normal lacrimal gland pathology in order to improve dry eye symptoms. Our approach focuses on antioxidant protection of the lacrimal gland, based on the rationale that elevated oxidative stress levels resulting from corneal inflammation contribute critically to lacrimal gland dysfunction. We employ a number of experimental paradigms, incl. in vitro and in vivo technologies to study dry-disease. A recent focus of the laboratory has been to improve and standardize the induction of dry-eye disease in in vivo models using a combination of environmentally-induced and scopolamine-induced symptoms.
Histopathology of healthy lacrimal gland stained with hematoxylin/ eosin (left). One week exposure to a desiccating combined with transdermal administration of scopolamine resulted in significant immune cell infiltration in the lacrimal gland (right).
Selected publications:
• Kaja S, Hilgenberg JD, Rybalchenko V, Medina-Ortiz WE, Gregg EV, Koulen P. Polycystin-2 expression and function in adult mouse lacrimal acinar cells. Invest Ophthalmol Vis Sci. 2011;52(8):5605-11. PMCID: 3176037.
• Kaja S, Hilgenberg JD, Rybalchenko V, Medina-Ortiz WE, Gregg EV, Koulen P. Polycystin-2 expression and function in adult mouse lacrimal acinar cells. Invest Ophthalmol Vis Sci. 2011;52(8):5605-11. PMCID: 3176037.