A profile of transcriptomic changes in the rd10 mouse model of retinitis pigmentosa

نویسندگان

  • Philip J. Uren
  • Justine T. Lee
  • M. Mehdi Doroudchi
  • Andrew D. Smith
  • Alan Horsager
چکیده

PURPOSE Retinitis pigmentosa (RP) is a photoreceptor disease that affects approximately 100,000 people in the United States. Treatment options are limited, and the prognosis for most patients is progressive vision loss. Unfortunately, understanding of the molecular underpinnings of RP initiation and progression is still limited. However, the development of animal models of RP, coupled with high-throughput sequencing, has provided an opportunity to study the underlying cellular and molecular changes in this disease. METHODS Using RNA-Seq, we present the first retinal transcriptome analysis of the rd10 murine model of retinal degeneration. RESULTS Our data confirm the loss of rod-specific transcripts and the increased relative expression of Müller-specific transcripts, emphasizing the important role of reactive gliosis and innate immune activation in RP. Moreover, we report substantial changes in relative isoform usage among neuronal differentiation and morphogenesis genes, including a marked shift to shorter transcripts. CONCLUSIONS Our analyses implicate remodeling of the inner retina and possible Müller cell dedifferentiation.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Blood flow and anatomical MRI in a mouse model of retinitis pigmentosa.

This study tested the sensitivity of an arterial spin labeling MRI method to image changes in retinal and choroidal blood flow (BF) and anatomical thickness of the retina in the rd10 mouse model of retinitis pigmentosa. High-resolution (42 × 42 μm) MRI was performed on rd10 mice and age-matched controls at 25, 35, and 60 days of age (n = 6 each group) on a 7-T scanner. Anatomical MRI was acquir...

متن کامل

Electrophysiological and Histologic Evaluation of the Time Course of Retinal Degeneration in the rd10 Mouse Model of Retinitis Pigmentosa

Among several animal models of retinitis pigmentosa (RP), the more recently developed rd10 mouse with later onset and slower rate of retinal degeneration than rd1 mouse is a more suitable model for testing therapeutic modalities. We therefore investigated the time course of retinal degeneration in rd10 mice before adopting this model in our interventional studies. Electroretinogram (ERG) record...

متن کامل

Microglia-mediated IGF-I neuroprotection in the rd10 mouse model of retinitis pigmentosa.

PURPOSE To characterize the effect of IGF-I in the rd10 mouse model of retinitis pigmentosa at the cellular level, focusing on the role of microglia in the neurodegenerative process. METHODS Both organotypic retinal explants and intravitreal injections were used to assess the effect of IGF-I on photoreceptor cell death in the Pde6b(rd10) mice. Cell death was determined by TUNEL in retinal sec...

متن کامل

Receptor interacting protein kinase mediates necrotic cone but not rod cell death in a mouse model of inherited degeneration.

Retinitis pigmentosa comprises a group of inherited retinal photoreceptor degenerations that lead to progressive loss of vision. Although in most cases rods, but not cones, harbor the deleterious gene mutations, cones do die in this disease, usually after the main phase of rod cell loss. Rod photoreceptor death is characterized by apoptotic features. In contrast, the mechanisms and features of ...

متن کامل

Pharmacological Analysis of Intrinsic Neuronal Oscillations in rd10 Retina

In the widely used mouse model of retinal degeneration, rd1, the loss of photoreceptors leads to rhythmic electrical activity of around 10-16 Hz in the remaining retinal network. Recent studies suggest that this oscillation is formed within the electrically coupled network of AII amacrine cells and ON-bipolar cells. A second mouse model, rd10, displays a delayed onset and slower progression of ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 20  شماره 

صفحات  -

تاریخ انتشار 2014