The Royal College of Surgeons (RCS) rat with inherited retinal
dystrophy has been widely used as a model to study human retinal
degenerative diseases, such as retinitis pigmentosa (RP). It has been
shown that the retinal pigment epithelium (RPE) cell is affected by the
rdy − mutation and continuously expresses the
rdy − phenotype.
1 Histopathology
has shown that retinal degeneration starts within the first month after
birth and that most of the photoreceptor cells are lost in the next
month.
2 3 In terms of the pathologic molecular course of
retinal degeneration, it has been suggested that the inability of the
RPE to phagocytose shed tips of rod outer segments (ROS) debris in RCS
rats is primarily involved.
4 5 6 In contrast, RCS
photoreceptor cells are considered to be normal in structure and
functions, because RCS photoreceptor cells can survive retinal RPE
transplantation.
7 8 9 However, the deficit of phagocytosis
in RCS RPE cells is most likely to be ROS specific, because normal
capacity of the RCS RPE cells in phagocytosis of nonspecific
polystyrene latex spheres has been identified.
10 11 12 In
addition, several studies in vitro and in vivo have shown that the
ability of the RCS RPE cells to bind ROS is normal, but the ingestion
of bound ROS is significantly reduced.
6 13 14 15 These
observations allowed us to speculate that some unknown deficit in the
ROS may be involved in addition to the deficiency in phagocytosis in
the RPE. In fact, it has been found that several changes occur in RCS
ROS including opsin,
16 arrestin,
17 18 and ROS
protein phosphorylation levels,
19 suggesting that
the quenching of the phototransduction pathway might be
affected in RCS. In addition, other changes have been identified in
retinal proteins including heat shock protein (hsp)
70,
18 20 neurotrophic factors, fibroblast growth
factors,
21 and phospholipids.
22 However, it
is still ambiguous whether such changes are primary causes of the
diseases or secondary events associated with retinal degeneration, and
the relationship among these changes is unclear, because no systematic
studies have been undertaken, such as the mapping of retinal proteins.