Retinitis Pigmentosa (RP) is an inherited disorder that may lead to blindness. In the rhodopsin S334ter-line-3 rat model of RP, the death of rods induces spatial rearrangement of cones into regular ring mosaics. Using this model, we discovered that the ring mosaics are restored to a homogeneous distribution upon application of tissue inhibitor of metalloproteinase-1 (TIMP-1). In this study, we further investigated the cone migration and spatial distribution of second-order neurons and their connections to cones in the presence or absence of TIMP-1 using immunohistochemistry to identify retinal neurons and their connections with cones. M-opsin cell bodies and their outer segments were evaluated to determine whether TIMP-1 delays the degeneration of outer segments of cones. We observed that during cone rearrangement into ring mosaics in RP retina, dendritic processes of second-order neurons undergo remodeling to maintain their synaptic connections with the cones in the rings. TIMP-1 treatment induced the cones to rearrange and dendritic processes of second-order neurons to return to a more homogeneous spatial distribution. In addition, TIMP-1 treatment protected the outer segments of cones at later stages of retinal degeneration. Our findings clearly demonstrate that despite their dramatic spatial rearrangement, cones and second-order neuron processes maintain their synaptic connections before and after TIMP-1 treatment.
Bibliographical noteFunding Information:
We thank Dr. Matthew M. LaVail for kindly providing us with animals. The work was supported by a VSoE Research Innovation Fund to E-JL, and by National Science Foundation Grant 0310723 and National Eye Institute Grants EY016093 and EY11170 to NMG, and EY015851 to CMC, CMC is the inaugural Mary D. Allen Endowed Chair in Vision Research (Doheny Eye Institute), NEI core grant: EY03040 (Doheny Eye Institute), Research to Prevent Blindness (USC Ophthalmology), the Mary D. Allen Foundation (CMC) and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education ( 2014R1A6A3A03059828 ).
© 2015 Elsevier Ltd.
- Bipolar cell
- Cone mosaic
- Cone outer segment
- Horizontal cell
- Retinitis pigmentosa
- Synaptic protein
- Tissue inhibitor of metalloproteinase-1(TIMP-1)