The Purkinje cell degeneration (PCD) mutant mouse is characterized by a degeneration of cerebellar Purkinje cells and progressive ataxia. To identify the molecular mechanisms that lead to the death of Purkinje neurons in PCD mice, we used Affymetrix microarray technology to compare cerebellar gene expression profiles in pcd3J mutant mice 14 days of age (prior to Purkinje cell loss) to unaffected littermates. Microarray analysis, Ingenuity Pathway Analysis (IPA) and Expression Analysis Systematic Explorer (EASE) software were used to identify biological and molecular pathways implicated in the progression of Purkinje cell degeneration. IPA analysis indicated that mutant pcd3J mice showed dysregulation of specific processes that may lead to Purkinje cell death, including several molecules known to control neuronal apoptosis such as Bad, CDK5 and PTEN. These findings demonstrate the usefulness of these powerful microarray analysis tools and have important implications for understanding the mechanisms of selective neuronal death and for developing therapeutic strategies to treat neurodegenerative disorders.

The medical treatment of glaucoma has evolved significantly over the past several decades. The main driving forces behind this evolution are the safety profiles and efficacy of these medications. Prostaglandin (PG) analogues are shown to be superior to older drugs in both efficacy and tolerability. Though there are much fewer side effects that manifest after using PG analogues, the adherence and compliance to medication regimens are surprisingly lower than expected. A commonly sited reason is the ocular irritation and inflammation with these medications. Much of this inflammation can be attributed to the preservative, benzalkonium chloride (BAK). The chronic clinical and subclinical inflammation becomes increasingly detrimental when filtration surgery fails from bleb fibrosis secondary to this hypercellularity. A BAK-free formulation of a PG analogues recently became available. BAK-free travoprost is reviewed here. It has demonstrated equal efficacy and less ocular surface toxicity than its preserved counterparts. It is expected to serve as an instrumental resource in managing ocular hypertension and glaucoma in patients who demonstrate significant sensitivity to BAK. More randomized, controlled, double-blind studies are encouraged to evaluate its improved safety and tolerability.

Glaucoma, a group of eye diseases that share a characteristic pattern of deterioration of the optic nerve, is a leading cause of blindness internationally. The treatment options for this optic neuropathy continue to remain limited considering that patients may become refractory to either medical therapy or surgical intervention. The initial treatment of choice for most ophthalmologists is topical medical therapy. The goal of medical therapy is to reduce the intraocular pressures in an effort to either halt or slow the progressive deterioration of the optic nerve. However, topical therapy causes a spectrum of cellular responses that may lead to chronic conjunctivitis after the use of multimedication and/or long-term therapy. This chronic conjunctivitis may not only lead to intolerance to therapy, but is also attributed to a significant proportion of trabeculectomy failures due to scarring of the bleb. Since incisional surgery is a primary option for long-term management of glaucoma, particularly those patients with end-stage disease, it is important to investigate the presence of topical drug- mediated inflammation and its effects on further surgical failure.