Canine Ophthalmology

Simon Petersen-Jones, DVM, PhD; Michigan State University

 

The presentation will cover two main topics. Firstly the condition known as ocular melanosis in Cairn Terriers will be described. This condition is inherited, most likely in an autosomal dominant fashion and results in a slow proliferation of pigmented cells within the eyes of affected dogs. The pigment proliferation lead to a secondary glaucoma that results in blindness and pain. Aim of the research at Michigan State University into this condition (partly supported by AKC-CHF) is to identify the gene defect and develop a DNA-based test to allow eradication of the condition. Investigation of the reason that the cells are able to proliferate is also important and may shed some light on the general processes controlling pigmented cell growth and division. This may be important in other conditions involving cell proliferation. Furthermore, understanding the process may suggest some treatments to control the condition in affected dogs.

 

The second part of the talk will concentrate on advances in the treatments for hereditary retinal disease. Examples of gene therapy, and drug therapy for retinal disease will be provided and a mention will be made of what the future will have in hold for both humans and dogs with these conditions.

 

Biographical Profile

 

Dr. Simon Petersen-Jones is Associate Professor in Comparative Ophthalmology at Michigan State University. Following an ophthalmology residency he spent 6 years at the Royal (Dick) School of Veterinary Studies as Head of Ophthalmology Service. He then moved to University of Cambridge under a Wellcome Trust Veterinary Career Development Fellowship. This enabled him to pursue his research into progressive retinal atrophy for which he was awarded a PhD. Since 1998 he has been at Michigan State University where he divides his time between clinics, teaching and continuing his research into hereditary eye diseases.

 

Dr. Petersen-Jones' research has been supported by the following grants:

 

2031: Investigation of Candidate Loci for Progressive Retinal Atrophy in the Old English Sheepdog and Papillon Breeds of Dog

2442: Investigation of Candidate Locifor Progressive Retinal Atrophy

642: Investigation of the Genetic Mutations Underlying Progressive Retinal Atrophy 903-A: Candidate Gene Investigation of Cairn Terrier Ocular Melanosis

 

 

Canine Ophthalmology – conference notes

 

Ocular Melanosis in Cairn Terriers

            Heritable condition – Autosomal dominant condition

            Cairn terriers (other breeds as well?)

            Bilateral proliferation of pigmented cells within both eyes (the white areas)

            Slowly progressive disease

            Leads to secondary glaucoma – intractable

            Age of onset/rate of progression is variable

 

Need to identify genes

            So dogs can be identified before breeding

Understand mechanism of cell proliferation

Samples & info – email for address:

 

Canine Retinal Dystrophies

            Progressive Retinal Atrophy

                        -Major cause of blindness in dogs (over 100 breeds affected)

-Genetic heterogeneity – many different gene mutations which leads to recessive, dominant and x link forms of the disease

                        *Symptoms

                                    Initial loss of night vision (rod-led retinal degeneration)

                                    Later day vision progressively lost (cones die)

                                    Eventually totally blind  

            In Cardigans:

                        Autosomal recessive

                        Lack of rod mediated vision (day vision)

                        Slow loss of cone vision (night vision)

                        PDE6A mutation

                                    Light not converted to electrical message in rod

                                    Rods die rapidly

                                    Cones die more slowly

            Testing function of retina by electoretinography

 

            Day blindness (cone degenerations) – Achromatopsia

            Equivalent of Leber Cogenital Amaurosis

                        Causes blindness in young children

                        Very rare 3 in 10,000 in people

                        In briards, null mutation in RPE65 gene

                                    Marked day & night vision loss

                                    Marked reduction in retinal function – as tested w/ electroretinogram

                                    Slow degeneration of retina

Therapies for Retinal degenerations

            Gene therapy

-Gene replacement therapy – introduce a new copy of the defective gene, specific for each gene

-Gene therapy to introduce a therapeutic protein – introduce a gene with growth factor, more attractive to pharmaceutical companies

*dogs vision improved with these procedures and has been repeated in several different labs and tested by an electroretinogram.  Also test with an obstacle course and tests.

                                    How late will gene therapy work?

                                    Can both eyes be treated?

                                    Will there be an immune response to introduced gene product?

                                    How long will benefit last?

                       

            Pharmaceutical therapy

                        To slow down retinal degeneration    

                        Regular injections into eye – not good idea so a slow release method was worked

                                    Little side effects, great results and vision is restored

           

Transplantation – progenitor cells

            Stem cells treated to start differentiating into retinal cells

            Injected into subretinal space (didn’t make the connection)

            Some cells integrated before being injected and thus showed some function

            Implantation of retinal chip

 

Future for hereditary eye disease

            Rapid identification of causal gene mutations

            More DNA based tests to allow eradication of disease

            Theraupeutic interventions to save vision

                        Gene therapy

                        Drug therapy

                        Progenitor cell transplantation