Take A Peek At Our High-Throughput AMD Model

Many baby boomers are entering their twilight years at risk of losing their sight because of age-related eye diseases.

Among the most debilitating is age-related macular degeneration (AMD), the leading cause of blindness among people over the age of 55 in developed nations. In the United States alone, 13 million people are at some stage of the disease.¹ The “dry” form of AMD is the most common, affecting 85-90% of patients with advanced AMD.² It is characterized by the accumulation of deposits (drusen) between the retina and its blood supply (choroid), ultimately resulting in islands of dead retina (geographic atrophy).

Developing effective new treatments for dry AMD means that researchers need accurate safety and efficacy models to evaluate potential therapies. At MPI Research, our ophthalmology team has established a rodent model that applies blue light to generate pathological features mimicking dry AMD. This is a high-throughput in vivo model allowing Sponsors to gather data quickly and accurately, leading to better and faster decisions about compound candidates.

Let MPI Research “open your eyes” to the ways we can meet your study needs in ophthalmology with the following services:

Rodent Blue Light Damage Model

• Increased oxidative stress, creation of CEP adducts, and deposition of complement factors
• Broad, dynamic range between healthy and affected animals provides an opportunity for rank ordering the efficacy and dose responsiveness of candidate therapies
• Photoreceptor cell death in a regionally irregular pattern similar to geographic atrophy
• High-throughput in vivo model allows Sponsors to test a variety of administration routes—topical, intravitreal, systemic, subconjunctival, and subtenon
• Albino or pigmented rat strains may be tested
• Clinically relevant endpoints using technologies to assess retinal morphology and function:
  • Photoreceptor loss quantified using spectral-domain optical coherence tomography (SD-OCT)
  • providing high-resolution retinal layer measurements similar to histology but without the need for tissue harvesting
  • Electroretinograms (ERG) demonstrates retinal function based on A- and B- wave amplitudes
  • Model validated using known agent to provide protection against photoreceptor loss

Validation of the Blue Light Damage Model
The positive control article, 8-OH-DPAT, provides protection from blue light-induced photoreceptor loss based on OCT and ERG assessments of retinal morphology and function. The outer segment length was measured from a 30° OCT slice in the superior temporal retinal region at 20 and 50 microns from the optic nerve head.

Additional Ophthalmology Services at MPI Research

• Scientists with pharmaceutical industry experience in ocular drug development
• Ocular DMPK including drug concentration-time data for the full complement of anterior and posterior segment tissues and fluids using LC(GC)-MS-MS, LC high-resolution-
• MS-MS or LC radioactivity profiling
• Expertise in developing, validating, and customizing ocular disease models
• State-of-the-art technology platforms for ocular assessments of efficacy and ocular toxicology:
  • Electroretinography (ERG; GLP-validated)
  • Fundus photography and retinal angiography
  • Optical coherence tomography (OCT)
  • A variety of ocular administration routes

Contact Tom Vihtelic, DVM, PhD, at +1.269.668.3336, ext. 2266 or thomas.vihtelic@mpiresearch.comto learn more about how MPI Research can assist you with better, faster ophthalmic studies for your drug candidates.

²Basic Facts About AMD, AMD Alliance International, http://www.amdalliance.org/information_overview_basic_facts.html, accessed May 8, 2012.