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OCR for page 41
The ERG and Sites and Mechanisms of
Retinal Disease, Adaptation, and
Development
DONALD C. HOOD
INTRODUCTION
What do ambient lights, retinal disease, and the development of the
neonatal retinal have in common? One answer is that each can alter the
retina's sensitivity to light. A second is that the same noninvasive techniques
have been used with human subjects to assess the sites and mechanisms
of disease, adaptation, and developmental processes. One technique is the
recording of the electroretinogram (ERG). This paper presents a general
approach for using ERG data to assess the sites and mechanisms of a
change in retinal processing. The approach is illustrated using data from an
adaptation paradigm. Application to clinical and developmental questions
is considered. Since the receptor is the focus of this symposium, the
emphasis here is on testing the hypothesis that sensitivity changes that
accompany a disease, an adaptation process, or a developing retina have
their locus at the receptors.
The ERG is a gross potential recorded from the eye. Figure 1A shows
ERGs recorded from a normal adult. Each record is the response of the
eye to a flash of a different intensity. For higher flash intensities, the
characteristic a- and lo-waves of the ERG can be seen.
The ERG is a complex potential. The potential measured is actually
the algebraic sum of a number of individual components. Figure 2 shows
an analysis of the ERG by Brown (1968~. The analysis is similar to
Granit's classic analysis (Granit, 1947~. One of the two main potentials
contributing to the ERG is a corneally negative potential generated by
the receptors. This component was called p-III by Granit and is labeled
the rod late receptor potential in Figure 2. The two corneally positive
potentials, labeled D.C. component and lo-wave in Figure 2, were shown
41
-
OCR for page 42
42
DONALD C HOOD
Log I
-3.36
-3.03
-2.80
-2~
-2~34
-2~16-
-1 .99~
-1.76 _
1 e 51 __
,1 .49 _
-1~15-
-1 .08
-0~93
-0~66 _
-0~26-
me\
-1/15\\'~
50 msec
lOOyV
stimulus
FIGURE 1A ERG responses from a normal adult. Each record shows the response to a
single flash of light. The log of the flash intensity (log cd/m2)is shown next to each record.
SOURCE: Modified from Massof et al. (1984~.
OCR for page 43
ERG, RETINAL DISEASE, ADAPTATION, AND DEVELOPMENT
600
500
>
~ 400
-
. _
-
~ it, 200
(at
300
100
n
-
2 R m
f
I. .
R=~ R (')
I +/
7
o , ~ , ,
-40 -35
L91
by
R m
1 1 1
-30 -25 -20 -1 5 -1 0 -05 00 05
log I ( cd -see /m2 )
43
FIGURE 1B Intensity-response functions for the lo-wave. The filled symbols are the
peak-to-trough lo-wave amplitudes plotted against the log intensity of the flash. SOURCE:
Courtesy of M. Johnson.
by Brown to be generated by cells in the inner nuclear layer. These
potentials comprise Granit's p-II. The peak-to-trough amplitude of the
lo-wave provides a reasonably good measure of the magnitude of the po-
tentials generated in the inner nuclear layer. Some investigators measure
the a-wave to obtain information about the receptors. Use of the a-wave
as a measure of the magnitude of the receptor response is more risly or
rather requires additional assumptions.
The ERG was the focus of a great deal of research in the 194Qs, 1950s,
and 1960s. Many of the basic functions of the retina were inferred from this
wore As a laboratory technique, it has been supplanted for most purposes
by intracellular recording. In the clinic, however, the ERG still provides
a powerful tool for diagnosing the type and progression of retinal disease.
The development of the focal ERG and the use of quantitative analyses
have enhanced clinical interest in the ERG. Figure 1B illustrates one
quantitative approach. The filled symbols depict intensity-response data
from recordings such as those in Figure IN The smooth curve through the
data is given by Equation (1) in Figure 1, where R is the peak-to-trough
lo-wave amplitude, I is the flash intensity, K is the semisaturation constant,
and Rm is the maximum response. The exponent n is usually close to 1. To
simplifier the presentation, it is assumed that n is equal to 1.0.
Retinal diseases produce both an increase in K and a decrease in Rm.
Mary Johnson, Bob Massof, and I have been developing an approach to
OCR for page 44
44
DONALD C HOOD
S t i mulus ( 1 sec )
Predominantly ~ I \
rod ERG I,/ ~ Off-response
Rod l ~ t e receptor
potent i at
D. C. component-
\
b-~ave ~
Recant negat ivi ty
1 _-
FIGURE 2 An analysis of the components of the dark-adapted rod ERG. Repnnted
with permission from Vision Research, 8, Kenneth T. Brown, "The Electroretinogram: Its
Components and Their Origin," (if) 1968, Pergamon Press.
inferring the retinal site and mechanism of disease action from changes
in K and Rm (Johnson and Hood, 1988; Johnson and Massof, 1988~. To
evaluate this approach, I have analyzed adaptation data from Fulton and
Rushton (1978~. This analysis is summarized below.
INFERRING THE SITE OF ADAPTATION FROM ERG DATA
In the adaptation paradigm, intensity response data (as in Figure 1)
are collected for flashes presented on steady ambient lights. Fulton and
Rushton (1978) obtained intensity-response data for lo-waves recorded on
steady adapting fields ranging in intensity from no field (dark adapted) to
3.2 log scotopic trolands. They fitted Equation (1), with n set equal to 1.0,
to each set of intensity-response data.
1b illustrate our approach, assume that Fulton and Rushton's data are
well fitted by Equation (1) and that the rod system has been successfully
isolated. As the adapting intensity is increased, their intensity-response
curves move down and to the right when plotted as in Figure 1B. In terms
of Equation (1), the maximum response, Rm, decreases and the value of
the semisaturation constant, K, increases with increases in the intensity of
the steady adapting field. In Figure 3 the change in log Rm is plotted
against the change in log K. Each data point is for a different adapting field
intensity. The values of Rm and K are expressed relative to their dark-
adapted values. The value 0 log relative K or Rm represents no change
from the dark-adapted value (dashed lines). Data for the higher-adapting
intensities were omitted to help assure that the rod system was isolated
and to keep the range of sensitivity changes close to those seen below for
retinal diseases.
OCR for page 45
ERG, ATONAL DISEASE, ORATION, AD DE~LOPME
0.5 ~
0.0 ~
a:
~ -ns-
._
_
-
~v
-
lo
-1 .0 ~
-1.5 ~
~1
d.a. I
!
1
ll
. ~ ~ ~ ~
.8
-.4 .2
-2.0- I , . . . . .
-0.5 0.0 0.5 1.0 1.5 2.0
Log Relative K
45
FIGURE 3 Log relative Rm versus log relative K is shown for a range of adapting
intensities from the Fulton and Rushton (1978) study. The values of Rm and K, estimated
from their fit of Equation (1), are expressed relative to the dark-adapted values.
A Model of the ERG
Ambient lights produce a small decrease in Rm and a large increase in
K. How many of these changes can be attributed to the rod receptor and how
many to the cells of the inner nuclear layer? A simplified version (Johnson
and Hood, 1988) of the model we are developing is summarized in Table 1.
We assume that the pooled rod receptor response, A, is given by Equation
(2), where Ka is the semisaturation constant of the receptors and Am is the
maximum pooled response. Assume further that the response, B. of the
lo-wave generators in the inner nuclear layer is also described by a function
of the same form, where the pooled receptor response A is the input to
the lo-wave generator [Equation (3~. The parameters Kb and Bm are the
semisaturation constant and maximum amplitude of the lo-wave generators.
Finally, we assume that the peak-to-trough lo-wave amplitude measured is
proportional to the response of the lo-wave generators [Equation (4~. After
appropriate substitution and algebraic manipulation, Equation (5) shows
OCR for page 46
i
46
TABLE 1 Static Model of ERG
DONALD C HOOD
Pooled response of rod receptors:
Response of lo-wave generatom:
ERG lo-wave response:
by substitution
where
In
in + ran m
B = A + ~; Bm
R= pB
where ,0 is a constant
ln
l n ~ In m
Bum
Rm l+(I~i'b/Am)
I' via
(2)
(3)
(4)
(5)
(6)
(7)
that R. the lo-wave response one measures, has the form of Equation (1),
where Rm and K are given by Equations (6) and (7), respectively.
Notice that the semisaturation K and the maximum response Rm of
the lo-wave depends on three of the four parameters of the model. In other
words, changes in the receptor's semisaturation constant, Ka, only affect K
and changes in Bm only affect Rm. Both K and Rm are affected by the ratio
of Am to Kb. The dashed vertical and horizontal lines in Figure 4 show the
predicted changes in K and Rm for increases in Ka (a decrease in receptor
sensitivity) or a decrease in Bm (a decrease in the response amplitude of
the cells generating the lo-wave).
The semisaturation constant, Kb, of the lo-wave generator and the
maximum amplitude of the receptor potential, Am, both contribute to the
measured values of K and Rm [see Equations (6) and (7~. 1b obtain a
measure of the influence of Am and Kb on K and Rm, we can set the
ratio of Am/Kb in Equations (6) and (7~. A reasonable estimate of this
OCR for page 47
ERG, RETINAL DISEASE, ADAPTATION, AND DEVELOPMENT
0.5 -
E °°~
~ -0.5 -
._
co
-1 .0 -
o
-1 .5 -
-2.0 -
-0.5 o.o 0.5 1.0 1.5 2.0
i
Ka ~
`~,Bm 4'
Log Relative K
47
Am W orKbt
FIGURE 4 The data from Figure 3 are shown with theoretical curves based on changes
in the parameters of the model in Table 1.
ratio is about 102 5; it was obtained in the following way: The value of K
typically measured for the lo-wave is on the order of 102 5 times smaller than
the semisaturation of the receptors, Ka, measured for the a-wave (Fulton
and Rushton, 1978; M.A. Johnson, personal communication) or inferred
from human psychophysics (e.g., Sakitt, 1976; Hood and Greenstein, 1988a,
1988b). Substituting (lo-2 5) x Ka for K2 in Equation (7) provides a value
of the ratio Kb/Am. It too will be approximately 10-2 5. By specifying the
value of Kb/Am, Equations (6) and (7) provide estimates for changes in Rm
and K, with increases in Ka and decreases in Am.
The three solid curves in Figure 4 show the predicted changes in log
K and log Rm for increases in Kb or decreases in Am for three values of
the ratio Kb/Am. The middle curve was derived assuming a K/Ka ratio of
10-2 5. The two other solid curves are for K/K a ratios of 10-3 (upper solid
curve) and 10-2 (lower solid curved. Under these assumptions, an increase
in Kb or a decrease in Am largely affects K and has little effect on Rm.
[For a quantitatively similar analysis of the ERG, see Arden et al. (1983~.
For a quantitatively similar analysis of psychophysical data, see Hood and
Greenstein (Lomb). For the general notion that the rods are linear over a
wide range of conditions, see Rushton (1965~.]
OCR for page 48
48
DONALD C HOOD
How do we answer the question: Are the changes in K and Rm
produced by the steady adapting field occurring at the receptors? There
are two approaches one can take to answer this question: (1) an explicit
model of the receptors can be assumed or (2) the a-wave can be used to
obtain estimates of Ka and Am. Let us consider the first approach.
A Model of Adaptation of the Rod Receptor
The prevailing model of adaptation of the human rod receptor is
response compression.) Response compression as a model of receptor
adaptation was first described by Boynton and Whitten (1970~. More
recently, Baylor et al. (1984) have shown that this model fits the data from
single primate rods. Figure S is a summary of a response compression
model. The solid curve in the top panel is the dark-adapted intensity-
response function. Adapting fields, shown by dashed lines, are assumed
to produce responses as if they were flashes of light. The adapting-field-
induced desensitization of the receptor occurs because of the restricted or
compressed response range. When the total response is plotted versus the
total intensity of the adapting field plus the flash (see Figure SA), there is no
change in K or Rm. In the Fulton and Rushton experiment, an incremental
response, the ERG, was measured as a function of an incremental light, the
flash. The bottom panel in Figure 5B shows the predictions of a response
compression model in terms of incremental responses and incremental light
intensities. For this incremental response function, response compression
yields an increase in K and a decrease in Rm (Normann and Perlman,
1979~.
If a particular value of the dark-adapted Ka is assumed, the response
compression model provides predicted values of Ka and Am as a function of
adapting intensity. By substituting these values of Ka and Am in Equations
(6) and (7), the changes in Rm and K, relative to their dark-adapted values,
can be derived. The solid curves in Figure 6 show the predicted changes
in Rm (panel B) and K (panel A) assuming a response compression model
and a dark-adapted value for Ka of 102 3 scotopic trolands (td). The open
symbols, from Fulton and Rushton and Figure 3, are the changes in log
K (panel A) and log Rm (panel B) plotted as a function of adapting field
intensity. We can reject the receptor as the site of most of the sensitivity
1 In the clinical literature, "response compression" is often used to signify a decrease in response
amplitude without a change in K Here we use the term to mean a decrease in responsiveness
secondary to a decrease in the polarization of the receptor. The response compression model
described in Figure 5 results in an equal change in (log Ka) and ~—log Am) from their dark-
adapted values.
OCR for page 49
ERG, RETINAL DISEASE, ADAPTATION, AND DEVELOPMENT
Response Compression
O-
49
0
o
In
—2 -
CJ)
J
In
o
~ _,
to
it
c
ID
~ _ 3
O _ ~
—3 - 2
_, _
/
,, A,.
1
Log Total Intensity
=
1 1
1 1 1
1 1 1
1 1 1
1 1 1
1 1 1
1 1 1
1 1 1
1 1 1
1 1 1
1 1 1
1 1 1
1 ~ 1
1 1 1
1 1 1
1 1 1
1 1
1 1
1
1
~0
//
//
//
//
i/
//
_, o 1 2 3
Log Incremental (flash) Intensity
~ s 6
FIGURE 5 Response compression. The solid curve in the upper panel and the left-most
curve in the lower panel are the dark-adapted intensity-response functions for a hypothetical
receptor. The upper panel plots the total response amplitude versus the total light, flash
plus adapting field, for adapting fields of different intensities (dotted lines). The lower
panel shows the intensity-response functions in terms of the log of the incremental response
above the response of the adapting field versus the log of the incremental intensity above
the intensity of the adapting field. SOURCE: Adapted from Hood and F~nkelstein (1986~.
OCR for page 50
50
DONALD C. HOOD
changes occurring with light adaptation over the range of adapting intensi-
ties shown.2 From this analysis the changes observed in the semisaturation
constant, K, of the ERG can be largely attributed to an increase in Kb.
The small change in Rm can be attributed to changes in Bm.3
Using A-Wave Data to Estimate Ka and Am
As an alternative to assuming a model of receptor adaptation, we can
assume that the a-wave provides a measure of the receptor's response.
Fulton and Rushton (1978, their Figure 3a) measured intensity-response
functions for the a-wave. The a-wave amplitude is not easily measured in
all subjects or at all intensities. As a measure of the a-wave amplitude,
Fulton and Rushton used the slope of the a-wave. If we assume that this
measure is a good substitute for the rod receptor's response amplitude,
then their intensi~-response functions provide a measure of the change in
Ka and Am for each adapting intensity. Using Equations (6) and (7) and
the Fulton and Rushton values of Ka and Am for each adapting intensity,
the predicted changes in K and Rm attributable to receptor changes were
calculated. The small crosses in Figure 6 show the expected changes in log
K and Rm based on the observed changes in Ka and Am of the a-wave.
The conclusions from this analysis are the same; most of the change in K
is caused by an increase in Kb and the small change in Rm by a decrease
in Bm. (The agreement between the Fulton and Rushton a-wave data and
the response compression model of the receptors is better than it appears
in Figure 6. If the model were fitted to the a-wave data, the solid curve
in Figure 6A would be shifted vertically. Most of the variation from the
model is caused by the dark-adapted data point.)
Assessing the Approach
With both procedures for estimating Ka and Am, we reject the receptor
as the primary site of sensitivity change for adapting fields up to 1.4 log
scotopic trolands. In fact, we can conclude that the small changes in Rm are
attributable to changes in Bm of the inner nuclear layer lo-wave generators
and that the change in log K is largely due to an increase in Kb (cellular
adaptation in the inner nuclear layer). This is the conclusion we should
have expected from previous physiological and psychophysical work (see
Shapley and Enroth-Cugell, 1985, and Walraven et al., 1989, for reviews).
2This conclusion is restricted to the range of adapting intensities in Figure 6. At higher adapting
field values, the changes in Ka andAm make major contributions to changes in both K and Rm.
3According to the model, the difference between the solid curve and the data provide measures
of log Kb (panel A) and log Bm (panel B).
OCR for page 51
ERG, RETINAL DISEASE, ADAPTATION' AND DEVELOPMENT
A.
3.0
Y 2.0-
._
it_
1.0-
~:
o
._
o
B.
o.o -
-1.0
0.5 ~
0.0 ~
-0.5 ~
-1 .0 -
-1.5 ~
-2.0
m
LO
to
to
~ +
- 11 - ~
to
+ ~
d.a. -2.0 -1.0 o.o 1.0
Log Adapting Intensity (td)
~ ~ m b O
. . .. . . . . . . .
d.a. -2.0 -1.0 o.o 1.0
Log Adapting Intensity (td)
51
FIGURE 6 (A) Log relative Rm and (B) log relative K versus log adapting field intensities.
The values O log K or Bm represents a dark-adapted value. The open symbols are from
the Fulton and Rushton (1978) study. The solid curves are the predicted changes in log K
and log Rm based on the response compression model of the rod receptors. The crosses
show the predicted change in log K and log Rm derived from the Fulton and Rushton
a-wave data and Equations (6) and (7~.
OCR for page 52
52
DONALD C HOOD
The main purpose here, however, was not to test hypotheses about
rod system adaptation, but rather to evaluate an approach to inferring sites
and mechanisms of disease-related sensitivity changes from ERG data. If
the results of this analysis turned out to be inconsistent with previous work,
the ERG would not have been the topic of this paper. The results are,
however, encouraging. Let us consider the application of the approach to
the problem of retinal disease.
RETINAL DISEASE AND ERG CHANGES
Various retinal diseases have been shown to increase log K and de-
crease log Rm of the lo-wave. Figure 7 shows data from three clinical
studies. Each data point represents the log Rm and log K for a single
eye from a single patient. Open symbols are from two studies (Birch and
Fish, 1987; Massof et al., 1984) measuring ERGs of patients with retinitis
pigmentosa (RP), and the filled symbols are from a study examining the
ERGs of patients with central vein occlusion (Johnson and Hood, 1988~.
Both diseases decrease the maximum lo-wave response and increase the
value of K. However, the patterns of the results direr substantially. The
patients with central vein occlusion show relatively larger changes in K than
the patients with RP.
~ determine whether the changes in K and Rm are due to receptor
changes, the approach described above can be applied. We can assume a
model of receptor change and ask if it describes the changes in K and Rm,
or we can use a-wave recordings to obtain estimates of Ka and Am. RP
will be used to illustrate the first approach and central vein occlusion the
second.
Consider RP (filled symbols) first. RP is an inherited disease that
affects the pigment epithelium and thus the receptors. A loss in visual
pigment has been documented with both retinal densitometry and psy-
chophysical matching techniques. Histopathological studies show outer
segments that have been shortened and receptors that are twisted and dis-
torted. Ultimately the disease results in the loss of receptor cells. Ibble 2
lists seven hypothesized actions of RP on the receptors (labeled 2 through
8~. The other columns show the effects on the model's parameters (column
2) and the predicted changes in ~ and Rm (column 3~. Notice that except
for hypothesis 8 the receptor hypotheses translate into changes in Ka and
Am. And these changes in Ha and Am result largely in changes in K. Based
on these hypotheses, there should be little or no change in Rm.
Are the changes in K and Rm produced by RP occurring at the
receptors? Suppose we assume an explicit model of the receptor. If we
assume a value of Ka between 1.8 and 2.8 log scotopic trolands, the curves
labeled increased Ka and decreased Am in Figure 4 show the range of
OCR for page 53
ERG, RETINAL DISEASE, ADAPTATION, AND DEVELOPMENT
0.5 -
E o.o
~ ~.5-
~_
-
a: -1.0 -
a
-1.5
-2.0 -
-0.5 o.o
_ 1
porma
_ , ,_
_ _
. -
O.
~ .10
~ on
0= ~
° ~ ~
a
O0 0 0 ~
a
o
a a
a
· , · I · I
to
0.5 1.0 1.5 2.0
Log Relative K
53
FIGURE 7 Log relative Rm versus log relative K for ERG intensity-response functions
recorded from patients with retinal disease. Each data point is for a single eye of a
single patient. The filled symbols represent data from patients with central vein occlusion
(Johnson and Massof, 1988~. The open symbols represent data from RP patients from two
studies (Birch and Fish, 1987 squares; Massof et al., 1984~tnangles). The Rm and K
values are divided lay mean normal data for the RP patients and by the parameters for
the unaffected eye for the central vein occlusion patients. The 0.0 value represents normal
mean value or the value for the normal eye.
predicted changes in Rm and K for hypotheses 2 through 7 in Able 2. The
envelope of these curves is reproduced in Figure 7. We cannot reject the
receptor as the major cause of the change in log K.
Can we, however, reject the receptor as the only cause of the changes
in the ERG with RP? Hypotheses 1 through 7 can be rejected, as each
predicts little or no change in log Rm. A loss of visual pigment, shortened
or distorted receptors, or a decrease in the responsiveness of the receptors
cannot account for the ERG results. Only one receptor hypothesis is
capable of explaining the large decrease in log Rm. Hypothesis ~ in Table 2,
if coupled with one or more of the other receptor hypotheses, could in
theory account for the changes in both K and Rm. Large patches of receptor
OCR for page 54
54
TABLE 2 Hypothesized Disease Action and Predicted ERG Changes
DONALD C HOOD
Disease Action
Change
in Model
Predicted
lo-Wave
K Rm
Prereceptoral
1. Preretinal screening (e.g.,
cataract, increase in
macular pigment, blood)
Receptor
2.
Ha
Decreased quantal catch
Doss of pigment)
3. Decreased quantal catch
(misaligned or misshapened
receptors)
4. Shortening of outer segments
5. Random loss of receptors
6. Increased membrane potential
(response compression)
7. Decrease in response amplitude
8. Large regional loss of
receptors
IKa
Ha
Ha ]'Am?
MA
MA = OK
m a
lAm
JIB
m
normal (n)
n
n
An
An
An
An
n ~1
loss could lead to a loss of lo-wave generators and a decrease in both Bm
and Rm. However, the rod visual fields in these patients are probably too
large to produce a sufficient decrease in Bm based simply on a loss of
patches of receptors4 (Birch et al., 1987~. Although additional analyses of
field data must be done and electrical shunting must be considered, it is
likely that the ERG data will be consistent with recent psychophysical data
(Greenstein and Hood, 1986; Hood and Greenstein, 1988b) in supporting
an inner nuclear component to the sensitivity loss observed in RP.
4To generate predictions for a regional or patchy loss of receptors, a spatial dimension must be
added to the model in Table 1. Assume that there are a finite number of lo-wave generators and
that the response of each is given by
Bi = A + K Bm
for all i, where Ai is the pooled response of the receptors feeding into the ith lo-wave generator.
Note that we are assuming that all lo-wave generators have the same Kb and Bm. Assuming an
equal contribution of all lo-wave generators to the lo-wave recoded at the electrode, Equation (4)
becomes
R = ~ ~ pi
i
A patchy loss of receptors removes a subset of lo-wave generators by removing their receptor
pools. A loss of all the receptors contributing to A: eliminates the response of Bi. Under these
assumptions a regional loss of one-half of the visual field, by itself, would reduce log Rm by 0.3
log unit.
OCR for page 55
ERG, RETINAL DISEASE, ADAPTATION, AND DEVELOPMENT
55
The open symbols in Figure 7 represent data from patients with central
vein occlusion. In this disease the blood flow to the inner nuclear layer
of one eye is disrupted. The changes in K and Rm of this eye, relative
to the normal eye, are shown by the open square. Ophthalmologists must
determine which of these patients will go on to develop neovascularization
of the iris. Neovascularization not only leads to further loss of vision but
can also result in the loss of the eye. Johnson et al. (1988) have shown that
changes in the ERG, especially log K, are four times more sensitive than
fluorescein angiography in identifying patients at risk.
Are the large increases in log K due to receptor changes (Ka or Am) or
to changes in the inner nuclear layer (Kb)? Johnson and Massof (19~) have
analyzed a-wave data and found that the increase in log K is largely due to
an increase in Ka; that is, the increase in the semisaturation constant of the
lo-wave in these patients is largely due to an increase in the semisaturation
constant of the receptors. It appears that changes in receptor sensitivity
may be a good predictor of which patients will develop neovascularization.
This is particularly interesting since central vein occlusion disrupts blood
flow to the inner nuclear layer while leaving the choroidal blood supply of
the receptors intact. Disrupting the blood flow to the inner nuclear layer
appears to compromise receptor responsiveness.
DEVELOPMENT AND ERG CHANGES
Over the first 6 months or more of life the most fundamental of visual
capabilities, the detection of light, continues to improve. Fulton and Hansen
(1982) have measured ERG intensity-response functions of neonates. The
changes they measured in log Rm and log K for infants ranging in age from
1.5 to 12 months are shown in Figure 8 (filled symbols). The values of
Rm and K are expressed relative to the mean for a group of adults. The
adaptation data (open squares) from Figure 3 are shown for comparison.
The developmental data show larger changes in Rm for equivalent changes
in sensitivity than do the adaptation data. The theoretical curves are the
same as those in Figure 4.
From these data and the analysis above, we can reject the receptor as
the only cause for the developmental changes. Since the changes in Rm are
largely attributable to an increase in the response amplitude of the inner
nuclear layer cells, these ERG data suggest some postnatal development of
the inner nuclear layer. The nature of the postreceptoral development can
be further constrained by testing explicit hypotheses about the development
of the inner nuclear layer and by analyzing behavioral data (Hood, 1988~.
OCR for page 56
56
DONALD G HOOD
0.5 ~
0.0~
~ -0.5
CC -1 .0 -
lo
-1 .5 ~
-2.0 ~
adult
6mo ~
1
i
ll
1.5 mo
'' ~ ' 1 ' I ' 1 ' I
-0.5 0.0 0.5
1.0 1.5 2.0
Log Relative K
FIGURE 8 Log relative Rm versus log relative K for ERG intensity-response functions
recorded from infants. The filled symbols are for infants 1.5 to 12 months old and for
adults (from Fulton and Hansen, 1982~. The open symbols represent the adult adaptation
data from Figure 3. The smooth theoretical curves are the same as in Figure 4.
SUMMARY
The ERG is a complex potential; we should be cautious in interpreting
changes it brought about by disease or development. However, carefully
measured intensity-response functions combined with explicit models of
the ERG and with data from psychophysical paradigms (e.g., visual fields,
matching, increment threshold) provide the possibility of identifying sites
and mechanisms of disease action for specific diseases and individual pa-
tients.
. .
ACKNOWLEDGMENTS
This research was supported by National Eye Institute grant EY-02115
to D.C. Hood and V. Greenstein. I appreciate the helpful comments
OCR for page 57
ERG, RETINAL DISEASE, ADAPTATION, AND DEVELOPMENT
57
provided by M. Johnson, V. Greenstein, and D. Birch on an earlier version
of the manuscript and am particularly grateful to M. Johnson for her
tutorials and for reacquainting me with the ERG.
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Representative terms from entire chapter:
retinal disease
